Folate Receptor-Positive Circulating Tumor Cells as a Novel Diagnostic Biomarker in Non-Small Cell Lung Cancer (original) (raw)
Related papers
The Role of CTCs as Tumor Biomarkers
Advances in Experimental Medicine and Biology, 2015
Detection of Circulating Tumor Cells (CTCs) in peripheral blood can serve as a "liquid biopsy" approach and as a source of valuable tumor markers. CTCs are rare, and thus their detection, enumeration and molecular characterization are very challenging. CTCs have the unique characteristic to be non-invasively isolated from blood and used to follow patients over time, since these cells can provide signifi cant information for better understanding tumour biology and tumour cell dissemination. CTCs molecular characterization offers the unique potential to understand better the biology of metastasis and resistance to established therapies and their analysis presents nowadays a promising fi eld for both advanced and early stage patients. In this chapter we focus on the latest fi ndings concerning the clinical relevance of CTC detection and enumeration, and discuss their potential as tumor biomarkers in various types of solid cancers. We also highlight the importance of performing comparison studies between these different methodologies and external quality control systems for establishing CTCs as tumor biomarkers in the routine clinical setting.
Cancers, 2014
In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC 5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as
NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology
Journal of the National Comprehensive Cancer Network : JNCCN, 2011
The molecular analysis of biomarkers in oncology is rapidly advancing, but the incorporation of new molecular tests into clinical practice will require a greater understanding of the genetic changes that drive malignancy, the assays used to measure the resulting phenotypes and genotypes, and the regulatory processes that new molecular biomarkers must face to be accepted for clinical use. To address these issues and provide an overview of current molecular testing in 6 major malignancies, including glioma, breast cancer, colon cancer, lung cancer, prostate cancer, and acute myelogenous leukemia, an NCCN Task Force was convened on the topic of evaluating the clinical utility of tumor markers in oncology. The output of this meeting, contained within this report, describes the ways biomarkers have been developed and used; defines common terminology, including prognostic, predictive, and companion diagnostic markers, and analytic validity, clinical validity, and clinical utility; and pro...
2014
In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC 5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as
Circulating Tumor Cells and cfDNA: Key Predictive Biomarkers in Non - Small Cell Lung Cancer Progression and Treatment, 2023
Background/ Introduction: With the evolution of translational research in the realm of liquid biopsy, the relevance of circulating tumor cells (CTCs) and cfDNA or ctDNA is emerging. cfDNA is a fragment of DNA released into the plasma after cell apoptosis by lysis, carrying genome-wide DNA information. In contrast, ctDNA, a part of cfDNA, can be derived from primary tumors, metastases, and even CTCs. This novel approach has the potential for earlier lung cancer detection and monitoring of minimal residual disease (MRD) and resistance development, consequently paving the way for effective therapeutic decisions aimed at curing lung cancer. Materials and Methods: This article lays a comprehensive focus on CTCs as an advanced and validated marker in liquid biopsy. The ongoing research and discussions are targeted at attaining the new milestone of personalized (precision) medicine as a common standard of care for lung cancer. Results: The research findings indicate that CTCs, with their potential to serve as an effective biomarker in cancer, hold promise in recent advancements of cancer diagnosis and treatment. These cells could revolutionize the early detection and close monitoring of lung cancer, further informing appropriate therapeutic choices. Conclusion: The emerging utility of liquid biopsy, particularly CTCs and ctDNA, introduces a new dimension to personalized medicine in lung cancer treatment. The advancements summarized in this article highlight the promising prospects of this novel approach in achieving a standard of care in lung cancer, tailored to each patient's unique genetic profile.
Clinical Cancer Research, 2011
Purpose: Pathologic TNM staging is currently the best prognostic factor for non-small cell lung carcinoma (NSCLC). However, even in early-stage NSCLC, the recurrence rates after surgery range from 25% to 50%. The preoperative detection of circulating tumor cells (CTC) could be useful to tailor new therapeutic strategies in NSCLC. We assessed the presence of CTC in NSCLC patients undergoing surgery, using cytologic analyses, after their isolation by size of epithelial tumor cells (ISET method). The presence and the number of CTCs were considered and correlated with clinicopathologic parameters including patient follow-up. Experimental design: Of the 247 blood samples tested, 208 samples were from patients with resectable NSCLC and 39 from healthy subjects. The mean follow-up was 24 months. An image of detected cells with presumably nonhematologic features [initially defined as "circulating nonhematologic cells" (CNHC)] was recorded. The presence of CNHC was assessed blindly and independently by 10 cytopathologists, using cytologic criteria of malignancy on stained filters. The count of detected CNHCs was made for each filter. Results: One hundred two of 208 (49%) patients showed CNHCs corresponding to CNHC with malignant cytopathologic features in 76 of 208 (36%) cases. CNHCs were not detected in the control group. A level of 50 or more CNHCs corresponding to the third quartile was associated with shorter overall and disease-free-survival, independently of disease staging, and with a high risk of recurrence and death in early-stage I þ II-resectable NSCLC. Conclusion: A high percentage of NSCLC patients show preoperative detection of CNHC by the ISET method. The presence and level of 50 or more CNHCs are associated with worse survival of patients with resectable NSCLC. Clin Cancer Res; 17(4); 1-9. Ó2010 AACR.
Physical Biology, 2012
Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL −1 (range 0-515.6) and a mean of 44.7 ( ± 95.2) HD-CTCs mL −1 . No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III 8 Phys. Biol. 9 (2012) 016005 M Wendel et al (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early-and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients.
Journal of Thoracic Oncology, 2009
Background: Enumeration of circulating tumor cells (CTCs) may be valuable for lung cancer treatment and monitoring cancer patient relapse. In the present study we report clinical significance of lung cancer CTC. Methods: CTCs were enriched from peripheral blood of 47 lung cancer patients by means of a modified enrichment strategy, followed by identification with immunofluorescence staining using anticytokeratins 18 and 19 monoclonal antibodies. Results: A control group consisted of 18 healthy donors and 13 nonmalignant pulmonary tuberculosis patients had no positive subject detected. Among 41 newly diagnosed and 6 recurrent lung cancer patients (3 stage I-II, 22 stage III and 22 stage IV) including 27 adenocarcinoma (ADC), 7 squamous cell carcinoma and 13 small cell lung cancer (SCLC), positive detection rate of newly diagnosed patients with CTC Ն2/7.5 ml blood was 78% (ADC stage III), 75% (squamous cell carcinoma stage III) and 60% (SCLC stage III), respectively. Whereas 46% (ADC IV) and 71% (SCLC IV) were observed for stage IV patients. Recurrent patients showed highest detection sensitivity of 83%. A small scale follow-up study was performed on 12 patients following 2 courses of first line chemotherapy. This demonstrated a good correlation of CTC enumeration with radiographic response. Conclusions: Results of the present study suggest potential clinical utilities of CTC enumeration on lung cancer patients in terms of rapid evaluation of chemotherapy effect in real time and monitoring lung cancer recurrence. A large scale of study which is necessary for further validation of the significance of lung cancer CTC is being performed.