Preoperative Circulating Tumor Cells Research Articles

Circulating tumor cells and tumor DNA in patients with resectable colorectal liver metastases: The MIRACLE.

3011 Background: Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need for prognostic markers to detect minimal residual disease after local treatment. The aim of this study was to determine the association between recurrence-free survival (RFS) and detection of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) before and after surgical treatment of resectable CRLM. Methods: The MIRACLE isa prospective, observational biomarker study in patients with isolated, resectable CRLM without (neo)adjuvant chemotherapy, recruited between October 2015 and December 2021. The study was powered to detect at least a 20% difference in one-year recurrence rate between detectable and undetectable circulating tumor load after surgery. Blood samples were collected one day before surgery (T0) and three weeks (T3) after surgery. CTCs were enumerated using the FDA-approved CellSearch system. ctDNA before surgery was measured by next generation sequencing (NGS) using a targeted panel (Oncomine Colon cfDNA assay) and postoperatively by digital PCR (dPCR). Results: CTC enumeration resulted in positivity for 43 out of 192 patients (22%) at baseline and 14 out of 161 patients (9%) at T3. ctDNA was detected in 125 out of 191 patients (65%) at baseline, of which 25 (20%) still had detectable ctDNA at T3. Patients with postoperative undetectable CTC had a significantly improved RFS (1-year RFS: 15% vs. 51%, log-rank test p=0.009). Also, patients with postoperative undetectable ctDNA had a significantly improved RFS (1-year RFS: 20% vs. 54%, log-rank test p<0.001). In multivariable analysis, at baseline no association was found between RFS and CTCs (HR 1.01; p=0.97) or ctDNA (HR 1.29; p=0.29). In contrast, after surgery a significantly shorter RFS was observed in patients with detectable CTCs (HR 3.09; p=0.002) and ctDNA (HR 3.53; p<0.001). Postoperative ctDNA status was a stronger predictor of recurrence compared to known clinical risk factors. Conclusions: This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of detectable circulating tumor load after surgery on RFS. Postoperative ctDNA and CTC detection are a strong predictor for a shorter RFS after local treatment, as opposed to preoperative ctDNA or CTC detection. [Table: see text]

Circulating tumor cells help differentiate benign ovarian lesions from cancer before surgery: A literature review and proof of concept study using flow cytometry with fluorescence imaging.

Current tools are insufficient for distinguishing patients with ovarian cancer from those with benign ovarian lesions before extensive surgery. The present study utilized a readily accessible platform employing a negative selection strategy, followed by flow cytometry, to enumerate circulating tumor cells (CTCs) in patients with ovarian cancer. These counts were compared with those from patients with benign ovarian lesions. CTC counts at baseline, before and after anticancer therapy, and across various clinical scenarios involving ovarian lesions were assessed. A negative-selection protocol we proposed was applied to patients with suspected ovarian cancer and prospectively utilized in those subsequently confirmed to have malignancy. The protocol was implemented before anticancer therapy and at months 3, 6, 9 and 12 post-treatment. A cut-off value for CTC number at 4.75 cells/ml was established to distinguish ovarian malignancy from benign lesions, with an area under the curve of 0.900 (P<0.001). In patients with ovarian cancer, multivariate Cox regression analysis revealed that baseline CTC counts and the decline in CTCs within the first three months post-therapy were significant predictors of prolonged progression-free survival. Additionally, baseline CTC counts independently prognosticated overall survival. CTC counts obtained with the proposed platform, used in the present study, suggest that pre-operative CTC testing may be able to differentiate between malignant and benign tumors. Moreover, CTC counts may indicate oncologic outcomes in patients with ovarian cancer who have undergone cancer therapies.

Preliminary result of anatomical hepatectomy on recurrence based on preoperative circulating tumor cell status in hepatocellular carcinoma-update to august 2023

Preliminary result of anatomical hepatectomy on recurrence based on preoperative circulating tumor cell status in hepatocellular carcinoma-update to august 2023

Prognostic potential of preoperative circulating tumor cells to predict the early progression recurrence in hepatocellular carcinoma patients after hepatectomy

BackgroundThe role of circulating tumor cells (CTCs) in prognosis prediction has been actively studied in hepatocellular carcinoma (HCC) patients. However, their efficiency in accurately predicting early progression recurrence (EPR) is unclear. This study aimed to investigate the clinical potential of preoperative CTCs to predict EPR in HCC patients after hepatectomy.MethodsOne hundred forty-five HCC patients, whose preoperative CTCs were detected, were enrolled. Based on the recurrence times and types, the patients were divided into four groups, including early oligo-recurrence (EOR), EPR, late oligo-recurrence (LOR), and late progression recurrence (LPR).ResultsAmong the 145 patients, 133 (91.7%) patients had a postoperative recurrence, including 51 EOR, 42 EPR, 39 LOR, and 1 LPR patient. Kaplan–Meier survival curve analysis indicated that the HCC patients with EPR had the worst OS. There were significant differences in the total-CTCs (T-CTCs) and CTCs subtypes count between the EPR group with EOR and LOR groups. Cox regression analysis indicated that the T-CTC count of > 5/5 mL, the presence of microvascular invasion (MVI) and satellite nodules were the independent risk factors for EPR. The efficiency of T-CTCs was superior as compared to those of the other indicators in predicting EPR. Moreover, the combined model demonstrated a markedly superior area under the curve (AUC).ConclusionsThe HCC patients with EPR had the worst OS. The preoperative CTCs was served as a prognostic indicator of EPR for HCC patients. The combined models, including T-CTCs, MVI, and satellite nodules, had the best performance to predict EPR after hepatectomy.

Monitoring with circulating tumor cells in the perioperative setting of patients with surgically treated stages I-IIIA NSCLC.

Surgery is regarded as the treatment's cornerstone for early stage and locally advanced non-small cell lung cancer (NSCLC) whenever the tumor is considered resectable. Liquid biopsy is one of the most promising research areas in oncology in the last 10 years, providing a useful non-invasive tool to detect and monitor cancer. The prognostic value of circulating tumor cells (CTCs) has been studied in different cancer types and had been related with a higher risk of relapse and worse prognosis. The aim of this study is to evaluate the prognostic value of CTC detection in patients with stage I-IIIA NSCLC treated with surgery. We conducted a prospective, single-center study of 180 consecutive patients with resected and pathological confirmed stage I to IIIA (TNM AJCC/UICC 8th edition) NSCLC. Patients' blood samples were processed and CTCs were characterized before and after the surgery. A cohort of patients had CTC determination after chemotherapy and surgery. Cut-off points were established in 1 and 5 CTCs for statistical analysis. A proportion of 76.7% had at least 1 CTC before the surgery, and 30.6% had 5 or more, while 55.9% had at least 1 CTC after surgery, and 8.3% had 5 or more. We found no correlation between preoperative CTC detection for a cut-off of 5 with neither overall survival (OS) [hazard ratio (HR): 0.99, P=0.887], disease-free survival (DFS) (HR: 0.95, P=0.39) nor relapse (32.7% vs. 28.8%, P=0.596). We also did not find a correlation between postoperative CTCs detection for a cut-off of 5 with either OS (HR: 1.01, P=0.808), DFS (HR: 0.95, P=0.952) or relapse (26.7% vs. 29.5%, P=0.83). The mean change in the number of CTCs over time between preoperative and postoperative samples was 2.13, with a standard deviation of 6.78. Despite the large cohort of patients included in this study, CTC monitoring in the perioperative setting was not correlated with relapse, DFS or OS in our study, and therefore cannot be recommended as a reliable biomarker for minimal residual disease (MRD) after surgery.

Nomograms for postsurgical extrahepatic recurrence prediction of hepatocellular carcinoma based on presurgical circulating tumor cell status and clinicopathological factors.

Extrahepatic recurrence (EHR) is one of the major reasons for the poor prognosis of hepatocellular carcinoma (HCC). The present study aimed to develop and assess the performance of predictive models by using a combination of presurgical circulating tumor cell (CTCs) data and clinicopathological features to screen patients at high risk of EHR to achieve precise decision-making. A total of 227 patients with recurrent HCC and preoperative CTC data from January 2014 to August 2019 were enrolled. All patients were randomly assigned to one of two cohorts: development or validation. Two preoperative and postoperative nomogram models for EHR prediction were developed and multi-dimensionally validated. Patients with EHR had generally lower recurrence-free survival (p < 0.001), and overall survival (p < 0.001), and significantly higher CTC counts (epithelial CTCs, epithelial/mesenchymal hybrid CTCs, and mesenchymal CTCs count, all p < 0.05) than those without EHR. Univariate and multivariate analyses revealed that EHR was associated with four risk factors in the development cohort: total CTC count (p = 0.014), tumor size (p = 0.028), node number (p = 0.045), and microvascular invasion (p = 0.035). These factors were incorporated into two nomogram models (preoperative and postoperative), which reliably predicted EHR through multidimensional verification (e.g., calibration plot, receiver operating characteristic analysis, decision curve analysis, and clinical impact curve analysis) in the development and validation cohorts, respectively. With threshold of scores of 100.3 and 176.8 before and after surgery respectively, both nomograms were able to stratify patients into two distinct prognostic subgroups (all p < 0.05). The present study proposed two nomogram models integrating presurgical CTC counts and clinicopathological risks and showed relatively good predictive performance of EHR, which may be beneficial to the clinical practice of HCC recurrence. Further multicenter studies are needed to assess its general applicability.

Prognostic value of preoperative circulating tumor cells for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis

PurposeThe role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood.MethodsIn this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS).ResultsBefore and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC ≥ 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC ≥ 2 remained an independent predictor in all groups’ multivariate analysis.ConclusionWe discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.

Perioperative change of circulating tumor cells in cytoreductive radical prostatectomy for oligometastatic hormone-sensitive prostate cancer: the preliminary safety evidence from long-term oncologic outcomes.

Surgical manipulation has a risk of triggering the shedding of circulating tumor cells (CTCs) in patients with malignancies, However, perioperative change of circulating tumor cells in cytoreductive radical prostatectomy (CRP) for patients with oligometastatic hormone-sensitive prostate cancer (omHSPC) has not yet been well documented. This study aimed to assess whether CRP is a safe procedure for patients with omHSPC by monitoring the perioperative change of CTCs and investigating its impact on long-term oncologic outcomes. We have observed a significant decrease between the median CTC counts before and after surgery (6 vs. 4, p = 0.026). Comparing preoperative and postoperative CTC levels, seven patients increased (CTC increase group), one did not change and nineteen decreased (CTC non-increase group). PSA response rates in CTC increase group were lower than those in CTC non-increase group (73.0% vs 99.8%, p = 0.162), and nadir PSA was higher in CTC increase group (0.043 vs 0.003, p = 0.072). The CTC increase was positively correlated with the nadir PSA (r = 0.386, p = 0.047). The median follow-up period was 71.6months, we found that there was no significant difference in clinical-pathological, operative variables or long-term oncologic outcomes between perioperative CTC increase and non-increase groups. In the entire cohort, the CTC level significantly decreased after surgery. There was no significant differences in long-term oncologic outcomes between the CTC increase and non-increase groups, implying that CRP potentially represents a safe procedure for the treatment of patients with omHSPC. The results need to be confirmed in a prospective large-scale clinical trial.

A NOVEL NOMOGRAM TO PREDICT RESECTABLE GASTRIC CANCER BASED ON PREOPERATIVE CIRCULATING TUMOR CELL (CTC).

BACKGROUND Circulating tumor cells (CTCs) have been suggested to have an important prognostic role in gastrointestinal tumors. We developed a preoperative CTC-based nomogram to predict the prognosis of patients with resectable gastric cancer after surgery and established a risk stratification system based on the nomogram. METHODS From January 2012 to June 2017, we screened 258 gastric cancer patients treated with surgery from 1 center as the training cohort and 133 gastric cancer patients treated with surgery from another as the validation cohort, screened prognostic factors for the training cohort using univariate and multivariate COX risk proportional models, created predictive overall survival (OS) and recurrence-free survival (RFS) nomogram, and plotted the receiver operating curve (ROC) as well as the calibration curve for this nomogram in the training and validation cohorts. Risk score stratification was performed according to the nomogram, and overall survival (OS) survival curves were plotted for the low, medium, and high-risk groups using the Kaplan-Meier method. RESULTS The CTC positivity rate was 78.5% in all patients. CTC, TNM stage, and Ki-67 were the prognostic factors affecting OS and RFS after gastric cancer surgery. Nomogram consisted of these 3 variables. in the training group, the area under the curve (AUC) of nomogram at 1, 3, and 5 years OS were 0.918,0.829 and 0.813, respectively, and the area under the curve (AUC) for RFS was 0.900, 0884 and 0.839, respectively. There was a statistically significant difference in OS among the low, medium, and high-risk groups according to the risk stratification system constructed from nomogram scores (P<0.001). CONCLUSIONS Two nomograms based on preoperative CTC were established to predict overall and recurrence-free survival after resectable gastric cancer. The 2 nomograms had good discrimination and calibration and significant stratification ability of the risk stratification system established according to them.

The mesenchymal circulating tumor cells as biomarker for prognosis prediction and supervision in hepatocellular carcinoma

PurposeHepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Accurate prognosis prediction tools are urgently needed. While the use of circulating tumor cells (CTCs) as prognostic prediction tool has a clear potential.MethodsWe established a comprehensive, negative enrichment-based strategy for CTCs analysis in patients with HCC, involving identification of epithelial CTCs (E-CTCs) and mesenchymal CTCs (M-CTCs) through specific biomarker. This strategy was performed in 127 HCC cases, 21 nonmalignant liver disease (NMLD) patients and 42 health control to analyze the relevance between CTCs and tumor recurrence.ResultsThe total CTC number and M-CTC percent were positively correlated with tumor malignancy and high recurrence risk. Individually, preoperative total CTC number and M-CTC percent could robustly distinguish relapse cases from those with no relapse, with sensitivity of 80.95% and 90.48%, specificity of 74.12% and 84.71%, respectively. Levels of preoperative total CTC number and M-CTC percent can both be regarded as independent risk factors for HCC with early recurrence (P = 0.0053, P < 0.0001), and are both significantly correlated with worse recurrence-free survival (RFS) (log rank P < 0.0001; HR 7.78, 95% CI = 3.59–16.87; log rank P < 0.0001; HR 24.4, 95% CI = 8.67–68.77). The levels of total CTC number and M-CTC number had higher effectiveness than alpha fetal protein (AFP) in HCC longitudinal supervision (77.78% vs 88.89% vs 22.22%).ConclusionPreoperative and postoperative CTCs with higher effectiveness than AFP in prognosis prediction and recurrence supervision, indicating that CTCs could work as the biomarker for HCC clinical management.

High Platelet Count is a Potential Prognostic Factor of the Early Recurrence of Hepatocellular Carcinoma in the Presence of Circulating Tumor Cells.

Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs. 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves. A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥225×109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs >5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥225×109/L and CTCs >5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan-Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS). The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.

Preliminary Result of Anatomical Hepatectomy on Recurrence Based on Preoperative Circulating Tumor Cell Status in Hepatocellular Carcinoma

Preliminary Result of Anatomical Hepatectomy on Recurrence Based on Preoperative Circulating Tumor Cell Status in Hepatocellular Carcinoma

Circulating tumor cells as a preoperative risk marker for occult metastases in patients with resectable cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive tumor associated with a high rate of recurrence after resection. An important risk factor for recurrence is the presence of occult metasta-ses, which are not radiologically detectable at the time of diagnosis. There are currently no biomarkers for the preoperative assessment of micrometastases. A previous study demonstrated the prognostic relevance of circulating tumor cells (CTC) in patients with advanced CCA but the potential of CTCs as a preoperative marker for detecting occult metastases has not been investigated so far. In this two-phase study, we first recruited a cohort of 27 patients with histologically proven, metastatic CCA or gallbladder cancer (GBCA) to assess feasibility (feasibility cohort, FC). CTCs were measured in the peripheral blood using the CellSearch System (CSS) between October 2012 and January 2017. Subsequently, in 11 patients undergoing curative-intended resection for CCA (intrahepatic CCA: n =4; extrahepatic CCA n= 6; gallbladder cancer: n=1), peripheral and central venous blood specimens were obtained to improve detection rate by simultaneous measurement and to elucidate distribution of CTCs in different venous compartments. Presence of CTCs detection was correlated with postoperative TNM-status. In the FC, CTCs (range 1-3 cells, median: 1) were detected in 40% (11/27) patients and were signifi-cantly associated with worse overall survival (hazard ratio: 3.59; 95% CI: 1.79- 7.1; p = 0.04). By combined peripheral and central measurement, CTC detection was increased to 54% (6/11) in the resection cohort (RC) and was associated with metastases that were only identified during the surgical procedure (peritoneal carcinoma: n = 1; infiltration of the duodenum: n = 1) or immediately after surgery (evidence of pulmonary metastases by CT scan two days after resection, not evident on initial tumor staging prior resection). Taken together, in this single center pilot study, we demonstrated that CTCs are detectable in CCA patients and are associated with significantly impaired survival in patients at metastatic stage. Detection rate prior to surgery was improved to >50% by combined peripheral and central measurement. Moreover, preoperative CTC detection may indicate existing metastases and could help to stratify patients more accurately.

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients

PurposeTo investigate the value of circulating tumor cells (CTCs) and Ki-67 in predicting the prognosis of bladder cancer. Here, we tested CTC counts and Ki-67 levels to assess patient prognosis.Methods84 patients with bladder cancer who underwent surgery were included in this study. Peripheral blood CTCs were detected by SE-iFISH technology before and after surgery, and Ki-67 levels were analyzed by immunohistochemistry. The association between CTCs and Ki-67 and the combination of the two was analyzed to predict the prognosis of patients.Results76 out of 84 patients (90.5%) were positive. ROC curve analysis showed that preoperative and postoperative CTC counts = 4 and 2 were the best thresholds for predicting patient recurrence or death. In multivariate analysis, high postoperative CTC count (≥ 2) (P < 0.001) and Ki-67 high expression (≥ 15%) (P < 0.001) were independent poor prognostic factors for PFS in bladder cancer patients. In addition, the study found that Ki-67 levels were positively correlated with high postoperative CTC counts, Bladder cancer patients with Ki-67 high expression and high postoperative CTC counts were associated with extremely poor progression-free survival.ConclusionKi-67 high expression is associated with high postoperative CTC counts, both of which predict poor prognosis in bladder cancer patients.

107P Preliminary result of anatomical hepatectomy on recurrence based on preoperative circulating tumor cell status in hepatocellular carcinoma

Hepatocellular carcinoma (HCC), which comprises the majority of liver cancer was a leading cause of death worldwide. The high rate of recurrence severely hampers the long-term survival of HCC patients after hepatectomy. Early recurrence, which is mainly caused by intrahepatic dissemination, accounts for nearly 70% of all recurrent cases. Circulating tumor cells (CTC) has shown potential clinical implications. CTC was associated with the severity of microvascular invasion (mVI) in the peritumoral tissue.

Predictive Value of Circulating Tumor Cells Based on Subtraction Enrichment for Recurrence Risk in Stage II Colorectal Cancer.

Current guidelines recommend adjuvant chemotherapy (ACT) for stage II colorectal cancer (CRC) patients by using clinical high risk factors, with which circulating tumor cells (CTCs) were not considered. Here, an assessment to detect CTCs based on subtraction enrichment mediated by magnetic beads conjugated with CD45, immunofluorescence staining of CK, and fluorescence in situ hybridization of CEP8 is established. Both CEP8- and CK-positive CTCs have the potential to improve the risk stratification of stage II CRC patients. Patients with preoperative CTCs of ≥4 had a significantly higher recurrence risk than those with preoperative CTCs of <4 in two external validation cohorts (P < 0.0001). In the subgroup with clinical high risk, when preoperative CTCs were <4, patients did not benefit from ACT (P = 0.5764); however, when preoperative CTCs were ≥4, patients received benefit from ACT (P = 0.0064). Additionally, regardless of clinical risk status and preoperative CTC levels, if postoperative CTC levels were ≥4 for more than three consecutive time points (monitoring time interval, 2-6 months), the recurrence rate was 100%. Our findings suggested that the subtraction enrichment of CTCs could provide a reliable method to stratify the recurrence risk and make therapeutic decisions after surgery in stage II CRC patients.

Combination of Preoperative Circulating Tumor Cell Count and Neutrophil-Lymphocyte Ratio for Prognostic Prediction in Hepatocellular Carcinoma Patients after Curative Hepatectomy.

Background Both the preoperative neutrophil-lymphocyte ratio (NLR) and circulating tumor cell count (CTC) are associated with poor prognosis in hepatocellular carcinoma (HCC). The purpose of this study was to explore the prognostic value of these two indices (CTC-NLR) in HCC. Methods We retrospectively collected demographic and clinical data, including NLR and CTC, from 97 patients with HCC who underwent curative hepatectomy at our institution from March 2014 to May 2017. X-Tile software was used to confirm the optimal cut-off value of NLR and CTC for predicting overall survival (OS) in this study. OS were also analyzed using Kaplan-Meier and Cox regression methods. Based on preoperative CTC and NLR, patients were divided into three groups: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). Relationships of CTC-NLR with clinicopathological factors and survival were evaluated. Results Preoperatively, CTC positively correlated with NLR. Patients with NLR and CTC higher than the cut-offs had shorter OS than patients with low NLR and CTC. Kaplan-Meier analysis, and log-rank tests revealed significantly lower OS among patients with CTC-NLR scores of 0, 1, and 2. Uni- and multivariate analyses showed that CTC-NLR (hazard ratio 2.050, P = 0.005), CTC (hazard ratio 2.285, P = 0.032), and NLR (hazard ratio 1.902, P = 0.048) were independent predictor of OS. A time-dependent ROC curve indicated that the prognostic efficacy of the CTC-NLR at 1 year (0.714) was better than that of NLR (0.687) and CTC (0.590); the prognostic efficacy of the CTC-NLR at 2 years (0.746) was better than that of NLR (0.711) and CTC (0.601); the prognostic efficacy of the CTC-NLR at 3 years (0.742) was better than that of NLR (0.694) and CTC (0.629). Conclusions HCC patients with higher NLR and CTC tend to show shorter OS. Preoperative CTC-NLR may be associated with poor survival and might be a reliable prognostic predictor in HCC after curative hepatectomy.

Early ligation of the pulmonary vein can reduce the dissemination of shed tumor cells during thoracoscopic lobectomy

ObjectiveThe sequence of vessel ligation in lobectomy can significantly affect the hematogenous spread of circulating tumor cells (CTCs). Vein-first ligation substantially reduces CTC dissemination and achieves favorable survival compared with artery-first ligation. In this study, we further explored whether the timing of pulmonary vein (PV) ligation determined according to the early and late PV ligation technique is associated with CTC dissemination. MethodsA total of 44 patients who underwent uniform 2-port video-assisted thoracoscopic surgery lobectomy were enrolled; the subjects were divided into the early ligation group (n = 18) and late ligation group (n = 26) according to whether PV ligation was prioritized during surgery. PV blood was obtained before PV ligation and after lobe resection. CTCs were detected using telomerase reverse transcriptase-based CTC detection and validated using FlowSight and fluorescence in situ hybridization. ResultsThe median postoperative PV CTC (Post-PVCTC) count was 9 (interquartile range [IQR], 6-18), which was higher than the median preoperative PV CTC (Pre-PVCTC) count of 1 (IQR, 0-3; P < .001). Clinicopathologic correlation analysis showed that the Pre-PVCTC count correlated positively with TNM stage (P = .002) and lymph node metastasis (P = .002) and that the Post-PVCTC count correlated positively with tumor density (P = .043) and vessel/lymphatic invasion (P < .030). Interestingly, although no statistical difference in the median Pre-PVCTC count was observed, the median Post-PVCTC count in the early ligation group was 16 (IQR, 9.5-36.75), whereas that in the late ligation group it was 8 (IQR, 4.75-12.25), showing a significant difference (P = .004). ConclusionsWe provide the first evidence to show that early PV ligation can prevent PVCTCs from spreading into the circulation, offering an innovative surgical concept for the principle sequence of pulmonary vessel management.

Circulating tumor cells as a predictor for poor prognostic factors and overall survival in treatment naïve oral squamous cell carcinoma patients

The aim of this study was to investigate the presence of circulating tumor cells (CTCs) and their correlation with prognostic factors and clinical outcomes in treatment-naive patients with oral squamous cell carcinoma. CTCs were isolated using OncoDiscover technique from presurgically obtained peripheral blood of 152 patients with treatment naïve oral squamous cell carcinoma. Sensitivity analysis was performed by including 40 healthy controls. CTCs cutoff values for clinicopathologic factors were obtained from receiver operating characteristic curves. Multivariate models determined the significance of CTC as independent variables. Kaplan-Meier analysis differentiated in overall survival between CTC values corresponding to the stage. Sensitivity, specificity, and accuracy of CTC detection were 94.32%, 98%, and 95.17%, respectively. Platform differentiated true positives at >3.5 CTCs (P < .00001). CTCs above 20.5 were suggestive of nodal metastasis (P < .0001) with a linear trend for detecting occult metastasis (P=.061). Early and advanced stages could be differentiated by >13.5 CTCs (P < .0001). Elevated CTCs were significantly associated with extranodal extension (>21.45 CTCs, P=.025), perineural invasion (>19.35 CTCs, P=.049), and depth of invasion (>12.5 CTCs, P=.0038). Median survival was reduced by 19 months when CTCs were >13. Preoperative CTC levels demonstrated a strong correlation with adverse clinicopathology factors and suggested its role as a sensitive prognostic marker to predict survival outcome and disease progress.

Prognostic Role of Circulating Tumor Cells in Resectable Colorectal Liver Metastases

Background: A systematic review and meta-analysis was performed to assess the prognostic role of preoperative, intraoperative, and postoperative circulating tumor cells (CTC) in resectable colorectal liver metastases (CRLM). Methods: The following databases were searched in May 2021: Medline, Embase, Biosis, Cochrane, Web of Science, and clinicaltrials.gov. Resectable CRLM where CTC was detected using CellSearch® (FDA approved) or RT-PCR was included. A random-effects model was used for pooled and subgroup analyses of Disease-Free Survival (DFS) and Overall Survival (OS). Surgical resections performed for palliative purposes were excluded. Randomized and non-randomized clinical trial, and cohort studies were included. Hazard ratio (HR) along with confidence interval (CI) were extracted or calculated using the Tierney method. Study bias was assessed using the Newcastle-Ottawa (NOS) scale. Results: 10 studies (801 patients) were identified for qualitative analysis (Table 1). 9 studies (781 patients) were included in the pooled analysis, out of which 6 studies detected CTC using CellSearch®. Two studies were high quality based on NOS. There was no statistical difference in DFS in patients with preoperative CTC (HR 1.97; 95% CI 0.85 – 4.57), intraoperative CTC (HR 3; 95% CI 0.98 – 9.21), and postoperative CTC (HR 1.93, 95% CI 0.82 – 4.57) detected in peripheral blood with CellSearch®. The OS was worse in patients with preoperative CTC (HR 2.36, 95% CI 1.15 – 4.84) (Figure 1) but similar in patients with intraoperative CTC (HR 2.33, 95%, 0.79 – 6.83). Conclusion: Preoperative CTC detected in peripheral blood using CellSearch® may predict OS in patients undergoing liver resection for CRLM.