scholarly journals The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2613
Author(s):  
Eva Obermayr ◽  
Angelika Reiner ◽  
Burkhard Brandt ◽  
Elena Ioana Braicu ◽  
Alexander Reinthaller ◽  
...  

Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCscombo), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTCcombo-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, p < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16512-e16512
Author(s):  
V. Kolev ◽  
S. Mironov ◽  
O. Mironov ◽  
C. Moskowitz ◽  
N. M. Ishill ◽  
...  

e16512 Background: It has been hypothesized and shown in animal studies that the supradiaphragmatic lymph nodes serve as the principal nodes for lymphatic drainage of the entire peritoneal cavity. The purpose of this study was to determine the prognostic significance of enlarged supra-diaphragmatic nodes noted on preoperative computed tomography (CT) scan in patients with advanced epithelial ovarian cancer (EOC). Methods: We performed a retrospective chart review of all patients (pts) with FIGO stage III and IV EOC who had preoperative CT scans of the supradiaphragmatic region and primary cytoreductive surgery at our institution between 1997 and 2004. All scans were retrospectively reviewed by one board-certified radiologist (SM). To evaluate survival, Kaplan-Meier methods were used, with log rank Pvalues for comparisons. Results: A total of 212 eligible pts who underwent attempted primary cytoreduction followed by platinum-based systemic chemotherapy were identified for evaluation. With a median follow-up time of 52 mos, there were 135 deaths and a median overall survival of 48 mos (95% CI: 44–53). Of the 212 pts, 44 (21%) had supradiaphragmatic adenopathy with nodes >1 cm, while 168 (79%) did not have adenopathy in this distribution. None of the 44 pts with adenopathy had the enlarged nodes removed at primary cytoreduction. The median survival was 49 mos for pts with and 48 mos for patients without adenopathy (p = 0.46). In total, 155 (73%) patients underwent optimal cytoreduction (residual disease ≤ 1 cm). In the optimally cytoreduced pts, the median survival for the 125 pts without supradiaphragmatic adenopathy was 52 mos (95%CI: 45–59) compared to 51mos (95%CI: 41–58) for the 30 pts with supradiaphragmatic adenopathy (p = 0.33). Conclusions: Although a previous study has shown that supradiaphragmatic adenopathy was associated with poorer overall survival in EOC patients, our study did not confirm these findings. In our study, enlarged supradiaphragmatic nodes noted on preoperative CT scan did not have significant prognostic impact and therefore their clinical significance remains uncertain. No significant financial relationships to disclose.


Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 815
Author(s):  
Snezhanna O. Gening ◽  
Tatyana V. Abakumova ◽  
Dina U. Gafurbaeva ◽  
Albert A. Rizvanov ◽  
Inna I. Antoneeva ◽  
...  

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I–IV OC patients (median age 66 (Q1–Q3 53–70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01–0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02–1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
François-Clément Bidard ◽  
Lisa Belin ◽  
Suzette Delaloge ◽  
Florence Lerebours ◽  
Charlotte Ngo ◽  
...  

Introduction. In non-metastatic breast cancer patients, the REMAGUS02 neoadjuvant study was the first to report a significant impact of circulating tumor cells (CTCs) detection by the CellSearch system on the distant metastasis-free survival (DMFS) and overall survival (OS) endpoints. However, these results were only reported after a short follow-up. Here, we present the updated data, with a longer follow-up.Material and Methods. CTC count was performed before and after neoadjuvant chemotherapy in 118 patients and correlated to survival.Results. CTC count results were available before and/or after neoadjuvant chemotherapy in 115 patients. After a median follow-up of 70 months, detection of ≥1 CTC/7.5 mL before chemotherapy (N=95) was significantly associated with DMFS (P=0.04) and OS (P=0.03), whereas postchemotherapy CTC detection (N=85) had no significant impact. In multivariable analysis, prechemotherapy CTC and triple negative phenotype were the two independent prognostic factors for survival. We observed that the CTC impact is most significant during the first three years of follow-up.Discussion. We confirm that the detection of CTC is independently associated with a significantly worse outcome, but mainly during the first 3-4 years of follow-up. No prognostic impact is seen in patients who are still relapse-free at this moment.


2013 ◽  
Vol 128 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Eva Obermayr ◽  
Dan Cacsire Castillo-Tong ◽  
Dietmar Pils ◽  
Paul Speiser ◽  
Ioana Braicu ◽  
...  

2017 ◽  
Vol 90 (3) ◽  
pp. 256-261
Author(s):  
Iulian Claudiu Bădulescu ◽  
Elena Bărbuș ◽  
Doina Piciu

Thyroid cancer is a disease with a good prognosis and high survival rates, but having a marked growth of incidence all over the world in the last years. This fact requires special attention of researchers for understanding the behavior of this disease and to establish a correct therapy. Analysis of circulating tumor cells in patients with different malignancies is nowadays a new and exciting research tool, which can improve the diagnosis and prevent the metastatic disease. In the case of thyroid carcinoma there are few studies which explore these biomarkers and investigate the prognostic significance of circulating tumor cells. With this review we seek to emphasize the role of these cells to better understand the mechanisms of invasion or metastasis and to establish a new research base to treat aggressive forms of this type of cancer. Most of the included studies demonstrate the efficacy of these markers for diagnosis and follow up.


Oncotarget ◽  
2017 ◽  
Vol 8 (63) ◽  
pp. 106415-106428 ◽  
Author(s):  
Eva Obermayr ◽  
Natalia Bednarz-Knoll ◽  
Beatrice Orsetti ◽  
Heinz-Ulrich Weier ◽  
Sandrina Lambrechts ◽  
...  

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 147-147
Author(s):  
Nicolas Marie Guibert ◽  
Myriam Delaunay ◽  
Amellie Lusque ◽  
Sandrine Gouin ◽  
Nadia Boubekeur ◽  
...  

147 Background: Inhibitors of the immune checkpoint PD-1/PD-L1 have become a standard of care in NSCLC. Patient selection, currently based on PD-L1 expression in tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that monitoring PD-L1 staining of circulating tumor cells (CTCs) could represent a valuable non-invasive biomarker. Methods: Up to 3 blood samples were prospectively collected from patients with advanced NSCLC: i) pretreatment (nivolumab), ii) first follow-up, iii) progression. CTCs were isolated from 10 mL of blood using cell size-based technology (ISET, Rarecells). PD-L1 expression was assessed by immunofluorescence on CTCs and immunohistochemistry on tissue. Results: 162 samples from 96 patients were collected. PD-L1 expression could be assessed pretreatment on tissue and CTCs in 72% and 93%, respectively; and was ≥1% in 37% and 83%; ≥5% in 35% and 79%, respectively. No correlation between tissue and CTCs PD-L1 expressions was observed (Spearman coefficient correlation = 0.04, p = 0.77). At baseline, each 10/7.5 ml increase in CTCs count was associated with increased risk of death and progression (HR[95%CI]: 1.06 [1.005;1.117] p = 0.03 for OS and HR[95%CI]: 1.05 [1.01;1.10] p = 0.02 for PFS). The presence of PD-L1(+)CTC (≥1%) had no prognostic impact (OS: p = 0.89 and PFS: p = 0.55), but pretreatment PD-L1(+)CTCs were more frequent in the “non-responders” group (PFS < 6 months) (p = 0.04). Median CTC count was 30 (n = 96), 68.3 (n = 44) and 50.3 (n = 22) pretreatment, at the first follow-up and at progression, respectively. The changes in CTC count at the first follow-up had no impact on PFS (p = 0.45) or OS (p = 0.68). 96% of patients had PD-L1(+)CTCs at progression. Further analyses are ongoing to assess the prognostic value of the persistence of CTCs and PD-L1(+)CTCs at the first follow up and at progression. Conclusions: Analysis of PD-L1 expression on CTCs is highly feasible. PD-L1 expressions on tissue and CTCs are discordant, CTCs being more likely positives, suggesting false negatives occurring in small biopsies. Further analyses of the kinetics of this biomarker throughout ICI treatment, along with other circulating biomarkers, are ongoing. Clinical trial information: NCT02827344.


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