Number Of Circulating Tumor Cells In Patients Research Articles

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

Renal cancer is one of the most common malignant tumors of the urinary system, with distant metastasis occurring 30% of patients. Therefore, early detection and monitoring of tumor progression are of great significance in the diagnosis and treatment of renal cancer. However, current biomarkers used to diagnose, monitor recurrence and assess prognosis of renal cancer are still uncertain. Circulating tumor cells (CTCs) are tumor cells detached from the primary tumor or metastasis, invaded and existing in the peripheral blood, and are one of the most promising liquid biopsy targets because they can provide complete cell biological information. Microfluidic chip has advantages of miniaturization, high integration, and fast analysis, which has advantages in CTC separation and enrichment. In this study, 1 mL peripheral blood of each 30 patients with early localized renal cancer was collected before and 1 day after surgery. CTC enrichment was performed by microfluidic chip and CTCs were identified by immunofluorescence staining. All patients were followed up for a median of 17 months. The number of CTCs before surgery was higher than that after surgery (P<0.001), and the number was positively correlated with tumor-node-metastasis (TNM) stage and International Society of Urological Pathology (ISUP) grade. Patients in group CTC ≤2 had a longer progression-free survival (PFS) than those in group CTC ≥3 (P<0.05). Surgical treatment can remarkably reduce the number of CTCs in patients, and CTC counts can also play a role in monitoring tumor load and predicting prognosis in renal cancer.

Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology.

Metastasis, rather than the growth of the primary tumor, accounts for approximately 90% of breast cancer patient deaths. Microtentacles (McTNs) formation represents an important mechanism of metastasis. Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited targeted therapies. The present study aimed to isolate viable circulating tumor cells (CTCs) and functionally analyze them in response to drug treatment. CTCs from 20 TNBC patients were isolated and maintained in culture for 5 days. Biomarker expression was identified by immunofluorescence staining and VyCap analysis. Vinorelbine-induced apoptosis was evaluated based on the detection of M30-positive cells. Our findings revealed that the CTC absolute number significantly increased using TetherChips analysis compared to the number of CTCs in patients' cytospins (p = 0.006) providing enough tumor cells for drug evaluation. Vinorelbine treatment (1 h) on live CTCs led to a significant induction of apoptosis (p = 0.010). It also caused a significant reduction in Detyrosinated α-tubulin (GLU), programmed death ligand (PD-L1)-expressing CTCs (p < 0.001), and disruption of McTNs. In conclusion, this pilot study offers a useful protocol using TetherChip technology for functional analysis and evaluation of drug efficacy in live CTCs, providing important information for targeting metastatic dissemination at a patient-individualized level.

Circulating tumor cells (CTCs) as liquid biopsies in patients with metastatic colorectal cancer versus other GI malignancies.

192 Background: Most of the focus on liquid biopsies for patients with colorectal cancers and other solid tumors has been on circulating tumor DNA (ctDNA). Circulating Tumor Cells (CTCs) are the other less talked about liquid biopsies. This is due to need for real-time processing and handling of CTCs, and is less conducive on previously banked samples. We took this prospective discovery endeavor to report in real-time CTC analyses using 2 very different platforms in patients with colorectal and other GI cancers. Methods: CTCs were evaluated using 2 platforms: RareCyte, which is simplistically based on density of CTCs and unbiased selection/identification for enumeration/biomarker analyses, and Parsortix, which is based on size/compressibility of CTCs. All patients signed written informed consent. Up to 4 serial draws were done for each patient (Total = 150 draws; 281 test results). CTCs were identified using standard definitions of nuclear/epithelial markers. À la carte we selected PD-L1, HER2, EGFR, Ki-67, and where adequate, confirmation with panel based single cell sequencing was also performed. Cell cultures were attempted for the Parsortix collections. Results: Patients with colorectal cancer (CRC) had the highest number of CTCs (Mean: 15.8; Median: 7.5). This was in sharp contrast to the number of CTCs in patients with pancreatic cancer (PC) (Mean: 4.2; Median: 3). At least a third of patients with CRC had at least 3 CTCs. Another 17.4% and 11.4% had at least 10, and at least 20 CTCs in CRC; while no patients with PC had more than 20 CTCs. CTCs in clusters were also common at baseline. In addition, we detected a significantly lower number of CTCs from patients receiving treatment versus those were not (Median 2.7 versus 0.7). Striking differences were also observed in CTCs for those with untreated/progressive disease versus those who had responding/stable disease (Median of 2.7 versus 0). Biomarker analyses on HER2/PD-L1/Ki-67/EGFR were feasible when CTCs were detected. There was overall agreement on CTCs detected on either platform. Where available, single cell sequencing data was concordant with clonal aberrations on sequencing. Conclusions: This is one of the largest prospective real-time endeavors in patients with colorectal and other GI cancers providing data on CTCs as liquid biopsies using 2 very different platforms. The descriptive insights gained from processing, enumeration, kinetics, timing of collection, biomarker analysis, costs, comparison across tumor types, attempts at cell culture, and single cell sequencing are of value for studies and investigators considering the use of CTCs in patients with colorectal and other GI cancers. While most of the focus is on ctDNA-based platforms, CTCs offer a different lens from a liquid biopsy standpoint that is complimentary and worth developing further.

P-194 Circulating tumor cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies

“Liquid biopsies” are revolutionizing cancer care. The broad term often refers to identification of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in individuals with cancer. Most of the work pertaining to liquid biopsies has been about ctDNA. Data pertaining to work on CTCs as the other kind of liquid biopsies is scarce. Here we embarked on an effort to not only show feasibility of doing CTC enumeration and biomarker analyses, but also serial kinetics of CTCs in response to therapy in patients with colorectal cancer and other GI malignancies. This was a prospective study with collection and analyses of circulating tumor cells (CTCs) done in real-time in patients with colorectal cancer and other GI malignancies. We chose to identify CTCs using two different methodologies/platforms: RareCyte platform which relies on sepration based on the density of CTCs, and Parsortix platform which relies on the size/compressibility of CTCs. The study was reviewed by the institutional review board (IRB), and all patients (n = 59) signed a written informed consent before collecting blood samples at the University of Iowa Holden Comprehensive Cancer Center. Blood samples (4 tubes: 2 tubes for Parsortix system and 2 tubes for Rarecycte system) were collected from each patient at each time point. Each tube was subjected to CTC analysis and results averaged (Total = 150 draws; 281 test results) from all the patients. In addition to identification and enumeration of CTCs using standard definitions of nuclear/epithelial markers, additional biomarkers studied included PD-L1, HER2, EGFR, Ki-67, and where adequate confirmation with panel based single cell sequencing was also performed. Cell cultures were attempted for the parsortix collections. Patients with colorectal cancer (CRC) had the highest number of CTCs (Mean: 15.8; Median: 7.5). This was in sharp contrast to the number of CTCs in patients with pancreatic cancer (PC) (Mean: 4.2; Median: 3). At least a third of patients with CRC had at least 3 CTCs. Another 17.4% and 11.4% had at least 10, and at least 20 CTCs in CRC; while no patients with PC had more than 20 CTCs. In addition, we detected a significantly lower number of CTCs from patients receiving treatment versus patients not receiving treatment (Median 2.7 versus 0.7). Striking differences were also observed in CTCs for those with untreated/progressive disease versus those who had responding/stable disease (Median of 2.7 versus 0). Biomarker analyses on 4 markers HER2/PD-L1/Ki-67/EGFR were feasible when CTCs were detected. There was overall agreement on CTCs detected on either platform. Not suprisingly, the agreement was higher when more CTCs were detectable. Where available, single cell sequencing data was concordant with clonal aberrations on ctDNA/tissue NGS sequencing. This is one of the largest prospective endeavors in GI cancers showing feasiblity and value of capturing and analyzing CTCs in a prospective fashion using two very different platforms. Timing is key to CTC based protocols and analyses. Varied downstream capabilities of different platforms and the fact that they are capturing an overlapping but different bucket of CTCs lends pros and cons to each approach.

Application of Circulating Tumor Cells in Peripheral Blood in Judging the Prognosis of Patients with Renal Cancer and Related Indexes of Blood Coagulation

Objective: To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. Methods: 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. Results: There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). Conclusion: The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.

Proinflammatory cytokines and circulating tumor cells in ovarian cancer patients treated with platinum-containing chemotherapy

Summary. Circulating tumor cells (CTCs) are a potential source of tumor progression. Systemic tumor-associated inflammation can influence the cancer prognosis both independently and by changing the characteristics of CTCs. Data on the role of proinflammatory cytokines and CTCs in the ovarian cancer (OC) chemosensitivity are few and contradictory. Aim of the study. To assess the IL-17A, IL-18 levels and the number of CTCs in primary patients with OC before treatment and after 3 courses of standard platinum-containing chemotherapy, and the possibility of using these cytokines as a marker of the presence of CTCs. Materials and methods. The study included 72 patients with OC. The comparison group included 16 patients with benign ovarian tumors, the control group included 20 healthy women. The number of CTCs (CD45-/EpCam+/CK+) was determined immunofluorometrically before and after 3 courses of chemotherapy. The content of cytokines was assessed by ELISA. Statistica 13.0, jamovi 1.6.5.0 were used for data processing. Results. The level of IL-17A in blood in the benign tumors group was increased in comparison with OC (р=0.012) and control (р=0.042). The content of IL-17A increased over time in the subgroup of adjuvant chemotherapy (р=0.017). During treatment, IL-17A was higher among patients with platinum-sensitive tumors than with non-sensitive ones (р=0.054). High levels of IL-18 before treatment were associated with the development of platinum-refractory relapse (р=0.014). IL-18 levels before (р=0.027) and during treatment (p=0.052) were lower in patients with cytoreductive surgery in first line of treatment. Progression-free survival (PFS) (p = 0.012) and overall survival (OS) (p = 0.030) were lower in the cluster with high IL-18 and pretreatment leukocyte counts than in the cluster with low scores. Higher quantity of the pretreatment CTCs was associated with longer PFS in a multivariate analysis (HR 0.82 95% CI 0.69–0.98, р=0.028). The number of CTCs before treatment greater than 5 was associated with a decrease in OS (HR 1.31, 95% CI 0.98–1.73, р=0.064). Conclusions. A high level of IL-17A in the blood during treatment is associated with more favorable clinical characteristics of OC, while a high level of IL-18 in the blood before treatment is associated with less favorable characteristics and a worse prognosis. The number of CTCs in patients with OC is not related to the blood levels of IL-17A and IL-18. A greater number of CTCs before treatment in OC is associated with an increase in PFS, but a decrease in overall survival.

BIOL-04. CYTOPLASM PROTEIN GFAP MAGNETIC BEADS CONSTRUCTION AND APPLICATION AS CELL SEPARATION TARGET FOR BRAIN TUMORS

BackgroundIt is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. ResultsOur data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue. ConclusionsThe results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.

Cytoplasm protein GFAP magnetic beads construction and application as cell separation target for brain tumors

BackgroundIt is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed.ResultsOur data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue.ConclusionsThe results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.

Detection of Circulating and Disseminated Neuroblastoma Cells Using the ImageStream Flow Cytometer for Use as Predictive and Pharmacodynamic Biomarkers.

Circulating tumor cells (CTCs) serve as noninvasive tumor biomarkers in many types of cancer. Our aim was to detect CTCs from patients with neuroblastoma for use as predictive and pharmacodynamic biomarkers. We collected matched blood and bone marrow samples from 40 patients with neuroblastoma to detect GD2 +/CD45- neuroblastoma CTCs from blood and disseminated tumor cells (DTCs) from bone marrow using the Imagestream Imaging flow cytometer (ISx). In six cases, circulating free DNA (cfDNA) extracted from plasma isolated from the CTC sample was analyzed by high-density single-nucleotide polymorphism (SNP) arrays. CTCs were detected in 26 of 42 blood samples (1-264/mL) and DTCs in 25 of 35 bone marrow samples (57-291,544/mL). Higher numbers of CTCs in patients with newly diagnosed, high-risk neuroblastoma correlated with failure to obtain a complete bone marrow (BM) metastatic response after induction chemotherapy (P < 0.01). Ex vivo Nutlin-3 (MDM2 inhibitor) treatment of blood and BM increased p53 and p21 expression in CTCs and DTCs compared with DMSO controls. In five of six cases, cfDNA analyzed by SNP arrays revealed copy number abnormalities associated with neuroblastoma. This is the first study to show that CTCs and DTCs are detectable in neuroblastoma using the ISx, with concurrently extracted cfDNA used for copy number profiling, and may be useful as pharmacodynamic biomarkers in early-phase clinical trials. Further investigation is required to determine whether CTC numbers are predictive biomarkers of BM response to first-line induction chemotherapy.

Utility of Liquid Biopsy (CTCs) after Liver Transplantation in Cirrhotic Patients with Hepatocarcinoma

Introduction New markers associated with angiogenesis and tumor metastasis, such as circulating tumor cells (CTCs), are opening up new avenues in cancer management from the laboratory. The Aim of this work is to determine the number of CTCs in patients included in waiting list for liver transplantation of hepatocellular carcinoma and to study its possible association with the alpha fetoprotein tumor marker (AFP) and with clinical variables such as number of tumors, presence of tumor vascular invasion, waiting list time, time from diagnosis and post-transplant tumor recurrence. In addition, we intend to compare the pre-transplant levels of CTCs with those obtained one month, six months, one year and two years after the transplant. Materials and Methods Peripheral blood of 36 patients suffering hepatocellular carcinoma once included in waiting list for liver transplant was obtained. 29 of them were transplanted, 27 of whom had blood extracted one month after the transplant, 19 of them after 6 months and one year after the transplant and 11 of them two years after the transplant. In order to study the correlation between the concentration of CTCs and the concentration of AFP, number of tumors, time on waiting list and from diagnosis in the patients, the Rho Spearman test was used. The study of the association of the CTCs levels with vascular invasion and presence of post-transplant recurrence was conducted with Mann-Whitney U test. For the variation in the levels of CTCs before and after the transplant, the Wilcoxon (SPSS 15.0) test was used. Results The average concentration of CTCs in the 36 patients before transplant was 11.50 CTCs/10mL (RI=2.25-42). A statistically significant positive correlation was found between the pre-transplant levels of CTCs and the days on waiting list (Rho= 0,376 p=0,024). The CTCs were not correlated in a significant way with the AFP concentration, number of tumors and time since diagnosis. (p>0,05). Out of the 29 transplanted patients, 2 showed vascular invasion in liver. Differences in the levels of CTCs were found between the patients with and without vascular invasion (U=0,00 p=0,020), these being significantly higher in the patients with vascular invasion. However, no significant differences were found in the levels of CTCs of the patients with recurrence after transplantation (4 patients) as opposed to those who didn’t (U=42 p=0.611). Conclusions Our conclusion is that the levels of tumor cells in peripheral blood could be an unfavourable prognostic factor associated to longer waiting times and to the presence of vascular invasion by tumor with an increased risk of relapse and post-transplant metastasis. In addition, we can see how their levels decrease significantly after transplantation. However, it would be necessary to increase the number of patients in the study, as well as the follow-up time, in order to achieve greater clinical evidence for its utility.

Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Background/Aims: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence–in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). Methods: In this prospective study, we enrolled 72 patients with DTC before they underwent ¹³¹I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE–iFISH technique. CTC was defined by the aneuploidy. Results: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM⁺) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM^-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM⁺ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to ¹³¹I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM⁺ DTC (P< 0.001). Conclusion: We found CTCs ≥ 5 to be a potential predictive index for DM⁺ DTC; and CTCs ≥7 as a possible indicator of poor response to ¹³¹I treatment and worse prognosis in DM⁺ DTC.

Abstract 479: Detection and clinical significance of circulating tumor cells in squamous cell carcinoma of the head and neck

Abstract Background: With a developing tumor, tumor cells shed a variety of substances into the blood stream, such as tumor cells, tumor DNA, or exosomes, and these are considered to be as attractive circulating biomarkers to monitor disease progression in cancer patients. However, impact of circulating tumor cells (CTCs) in squamous cell carcinoma of the head and neck (SCCHN) is still not fully understood. In this study, we show that CTCs are present in the peripheral blood of patients with SCCHN, and then investigate the correlation with clinicopathological factors. Materials and Methods: 7.5mL of peripheral blood was obtained from 32 patients with pathologically and clinically confirmed SCCHN. Samples were run with a CellSieve™ Microfiltration Assay (Creatv MicroTech, Inc., Rockville, MD) using a low-pressure vacuum system. The CTCs captured by the filter were stained with an antibody mixture of FITC-conjugated anti-CK 8, 18, and 19, PE-conjugated anti-EpCAM, and Cyanine 5-conjugated anti-CD45. Cells that stained positive for DAPI and CK but negative for CD45, were identified as CTCs. Results: The CTCs were found in 29 (90.6%) of 32 patients. Although there was no association between the number of CTCs and tumor sites, the number of CTCs in patients with advanced disease (stage III/IV) was significantly increased, as compared with those with early disease (stage I/II) (p&amp;lt;0.05). Furthermore, patients with T3/4 had higher number of CTCs compared to patients with T1/2 (p&amp;lt;0.01). Meanwhile, nodal status was not significantly associated with the number of CTCs. In 12 of 32 patients tested, the number of CTCs after treatments was also evaluated. As expected, the number of CTCs was significantly decreased after treatments, regardless of the treatment modalities. Conclusion: Our results suggest that microfiltration is very efficient in capturing CTCs from SCCHN patients. Moreover, CTCs analysis in SCCHN may provide useful information for assessment of treatment efficacy. Citation Format: Kazuaki Chikamatsu, Hideyuki Takahashi, Koichi Sakakura, Minoru Toyoda. Detection and clinical significance of circulating tumor cells in squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 479.

MP49-07 THE RISK OF POSTOPERATIVE VENOUS THROMBOEMBOLISM ACCORDING TO THE CIRCULATING TUMOR CELL STATUS IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2016MP49-07 THE RISK OF POSTOPERATIVE VENOUS THROMBOEMBOLISM ACCORDING TO THE CIRCULATING TUMOR CELL STATUS IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY Armin Soave, Sabine Riethdorf, Roland Dahlem, Lars Weisbach, Valentin Maurer, Oliver Engel, Sarah Minner, Klaus Pantel, Margit Fisch, and Michael Rink Armin SoaveArmin Soave More articles by this author , Sabine RiethdorfSabine Riethdorf More articles by this author , Roland DahlemRoland Dahlem More articles by this author , Lars WeisbachLars Weisbach More articles by this author , Valentin MaurerValentin Maurer More articles by this author , Oliver EngelOliver Engel More articles by this author , Sarah MinnerSarah Minner More articles by this author , Klaus PantelKlaus Pantel More articles by this author , Margit FischMargit Fisch More articles by this author , and Michael RinkMichael Rink More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.420AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urothelial carcinoma of the bladder (UCB) patients are at a relevant risk for venous thromboembolism (VTE) following radical cystectomy (RC). In other cancer entities, circulating tumor cells (CTC) are associated with an increased risk of VTE. To evaluate whether the presence of CTC is associated with an increased postoperative risk of VTE and surgical complications in UCB patients treated with RC. METHODS We included 201 UCB patients treated with RC with bilateral pelvic lymphadenectomy without neoadjuvant chemotherapy at an academic center between 2007 and 2014. Preoperatively collected blood samples (7.5 ml) were analyzed for CTC using the CellSearch® system (Janssen, USA). Postoperative VTE was defined as clinically apparent venous thrombosis and/or pulmonary embolism following RC, and was confirmed by diagnostic imaging studies. Data on postoperative VTE and complications were collected retrospectively by patients' chart review. Postoperative complications were classified according to the Clavien-Dindo classification of surgical complications. Clinico-pathologic features were correlated with the VTE status and the CTC status. RESULTS Prior to RC, 54 patients (26.9%) had presence of CTC (mean CTC number: 4.9±31.3 (standard deviation (SD); median: 0; range: 0-372). Within 30 days postoperatively, 6 patients (3.0%) had VTE, and 136 patients (67.7%) had any surgical complication. The most frequent complications were Clavien-Dindo grade 1 and 2 complications in 95 patients (47.3%), followed by grade 3 complications in 25 patients (12.4%) and grade 4 complications in 15 patients (7.5%), respectively. The presence of VTE was not associated with the CTC status or any other clinico-pathologic characteristics. There was no difference in the number of CTC in patients with VTE (mean CTC number: 1.0±1.5 SD) and without VTE (mean CTC number: 5.0±31.7 SD), respectively. The VTE status and the CTC status were not associated with surgical complications. The presence of CTC was associated with a positive soft tissue surgical margin, the presence of lymphovascular and micro-vessel invasion, and the administration of adjuvant chemotherapy (all p-values≤0.045). CONCLUSIONS While complications occur frequently within 30 days after RC, VTE are relatively rare events. Following RC, UCB patients with presence of CTC do not seem to be at an increased risk of VTE. In addition, the presence of CTC is not associated with surgical complications. However, a longer follow-up is urgently warranted. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e666-e667 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Armin Soave More articles by this author Sabine Riethdorf More articles by this author Roland Dahlem More articles by this author Lars Weisbach More articles by this author Valentin Maurer More articles by this author Oliver Engel More articles by this author Sarah Minner More articles by this author Klaus Pantel More articles by this author Margit Fisch More articles by this author Michael Rink More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Innovative method using circulating tumor cells for prediction of the effects of induction therapy on locally advanced non-small cell lung cancer

BackgroundThe existence of circulating tumor cells (CTCs) in patients with lung cancer has been reported. The purpose of this study was to assess whether CTCs are predictive of the pathological effects of induction chemoradiotherapy for patients with non-small cell lung cancer.MethodsPatients who underwent induction chemoradiotherapy followed by surgery were compared with those who underwent surgery alone. Peripheral and pulmonary venous blood samples from the involved lobe were collected intraoperatively, and the number of CTCs was counted using the CellSearch™ system, an epithelial cell adhesion molecule-based immunomagnetic technique.ResultsOf the 9 patients who underwent induction therapy, 4 achieved pathological CR, 4 achieved major response, and 1 achieved minor response. All patients who underwent induction therapy and surgery alone were negative for CTCs in peripheral blood. In the induction therapy group, 4 patients showing pathological CR were negative for CTCs in pulmonary venous blood (pvCTCs) and 5 showing major/minor response were positive (mean, 57.8 cells). The numbers of CTCs in patients showing major/minor response were significantly higher than those in patients showing pathological CR (p = 0.012, Mann–Whitney U test). All 6 patients undergoing surgery alone were positive for pvCTCs (mean, 207.5 cells), showing a significant difference from those undergoing induction therapy (p = 0.038).ConclusionsThe existence of CTCs in pulmonary venous blood reflects pathological non-CR, and therapeutic pathological response may be predicted by pvCTC measurement.

Detection of circulating tumor cells (CTCs) in patients with lung carcinoma by real-time fluorescent quantitative-PCR approach before and after chemotherapy

Circulating tumour cells (CTCs) are referred to the tumour cells that disseminated from the primary tumour and survive in circulating during the pro-ceeding of tumour growth. As surgical treatment evolves and local control has improved, the failure of cancer treatment has largely remained the re-sult of systemic metastasis. Selection of patients most likely to benefit from adjuvant strategies remains problematic. In order to develop a new standard of curative effect, this study was de-signed to track the number of CTCs in patients with lung cancer during chemotherapy. Methods: Samples of peripheral blood was taken from each lung cancer patients (n=32) on the day before chemotherapy as well as the third week after the chemotherapy cycle. The samples were subjected to real-time fluorescent quantitative reverse-tran- scriptase polymerase chain reaction (fqRT-PCR). Meanwhile the tumour size was determined by chest X-ray or computed tomograghy. Results Compared to that of pre-chemotherapy, the ex-pression level of cytokeratin (CK) 19 in the pa-tients significantly declined after chemotherapy (t=4.659,P=0.000). The level of CK19 mRNA in pa-tients with small cell lung cancer (SCLC) was higher than that of patients with non-small cell lung cancer (NSCLC) (t=1.944, P=0.061). The de-crease of CK19 mRNA level correlated well with the type during the treatment. Relatively the de-crease of SCLC is more obvious (t=6.073,P=0.000). The variation of CK19 mRNA level before and after chemotherapy was positively related to the dis-parity of tumour burden (r=0.593). There was also a significant association between the type (NSCLC vs. SCLC) and the change of tumour size (t=3.686, P=0.001).The positive rate before chemotherapy Supported by grant from the Natural Science Foundation in China (No.30972961). was 71.9% (23/32), while that after chemotherapy was 37.5% (12/32), indicating that 11 patients con- verted into negative after chemotherapy. Of the 16 patients which were in Ⅳ-stage, 11 cases were po- sitive (11/16,68.8%). Surprisingly, of the remaining 16 patients which were Ⅱ/Ⅲ stage, 12 cases were regarded as positive according to the criteria (12/6,75%). Conclusions: The real-time flu- ores-cent quantitative-PCR approach is useful for mea- suring the relative number of CTCs in a patients’ peripheral blood to monitor the effectiveness of treatment, and for designing more comprehensive and reasonable therapeutic regimes at earlier dates for patients. The treatment response can be immediately assessed by serial quantitation of CTCs after chemotherapy, and therefore this method highlights an alternative approach to rapidly access the patient’s response to treatment.