Detection of circulating tumor cells in bladder cancer patients

Nezos, Adrianos; Pissimisis, Nikolaos; Lembessis, Peter; Sourla, Antigone; Dimopoulos, Panagiotis; Dimopoulos, Theodore; Tzelepis, K.; Koutsilieris, Michael

doi:10.1016/j.ctrv.2008.11.003

Cited by 34 publications

(28 citation statements)

References 104 publications

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“…CTC have been documented in breast cancers where their enumeration is prognostic 20–22,73 , but have also been documented in colorectal cancers 25–27 , prostate cancers 23–24 , and other cancers 74–77 but not in healthy subjects or patients with non-malignant diseases 78 . CTC have been identified in ovarian cancers 28,29 , but their relation to prognosis has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study

Behbakht

Sill

Darcy

et al. 2011

Gynecologic Oncology

189

118

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Purpose Patients with persistent/recurrent epithelial ovarian cancer/primary peritoneal cancer (EOC/PPC) have limited treatment options. AKT and PI3K pathway activation is common in EOC/PPC, resulting in constitutive activation of downstream mTOR. The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor, temsirolimus in EOC/PPC and explored circulating tumor cells (CTC) and AKT/mTOR/downstream tumor markers. Methods Eligible women with measurable, persistent/recurrent EOC/PPC who had received 1–3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity. Primary endpoints were progression-free survival (PFS) ≥6-months, tumor response, and toxicity. CellSearch® system was used to examine CTC, and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry. Kendall’s tau-b correlation coefficient (r) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome. Results Sixty patients were enrolled in a two-stage sequential design. Of 54 eligible and evaluable patients, 24.1% (90%CI 14.9%–38.6%) had PFS ≥6 months (median 3.1 months), 9.3% (90%CI 3.7%–23.4%) experienced a partial response. Grade 3/4 adverse events included metabolic(8), gastrointestinal(8), pain(6), constitutional(5) and pulmonary(4). Suggested associations were between cyclin D1 and PFS ≥6 months, PFS or survival; positive CTC pre-treatment and lack of response; and high CTC expression of M30 and PFS ≥6 months/longer PFS. Conclusions Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC; however, PFS is just below that required to warrant inclusion in phase III studies in unselected patients. Cyclin D1 as a selection marker and CTC measures merit further study.

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Section: Discussionmentioning

confidence: 99%

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study

Behbakht

Sill

Darcy

et al. 2011

Gynecologic Oncology

189

118

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“…There are two strategies employed in all the current immunological isolation procedures: epithelial cell-specific markers (epithelial cell adhesion molecule (EpCAM) and cytokeratins (CK)) generally expressed by nearly all the tumor cells from epithelial origin and tumor-specific markers (a-Fetoprotein, Her2-neu, MUC1/MUC2, mammaglobulin, and carcinoembryonic antigen (CEA)) expressed by a particular type of cancer (Sleijfer et al 2007). Immunomagnetic isolation is performed with monoclonal antibodies labeled magnetic microbeads and a basic magnet to fish out CTCs from leukocytes background by magnetic force, whose sensitivity is usually reinforced by applying an anti-CD 45-negative selection of leukocyte, such as MACS TM (magnetic activated cell sorting system (Miltenyi Biotec)) (Cohen et al 2008;Nezos et al 2009). One obvious merit of this technique is that it avoids cell lysis while CTCs are being isolated, which facilitates the following CTC count, immunocytochemistry, and immunofluorescence assays.…”

Section: Immunological Approachesmentioning

confidence: 99%

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Sun

Yang

Zhou

et al. 2011

J Cancer Res Clin Oncol

164

137

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“…A variety of methods for detecting CTCs have been developed including nested RT-PCR, which utilizes two pairs of PCR primers to amplify a single locus. PCR-based methods are considered highly sensitive and also to demonstrate strong specificity via the design of primers that detect mRNA expression of tumor-specific genes such as cytokeratin (CK)-20, uroplakin (UP) II, and epidermal growth factor receptor (EGFR) [13,14]. The CellSearch system is another commonly used technique that was recently approved by the US Food and Drug Administration (FDA) for CTC detection in patients with metastatic breast, colorectal, and prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

Msaouel

Koutsilieris

2011

BMC Cancer

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BackgroundThe diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease.MethodsStudies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated.ResultsOverall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26).ConclusionsCTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests.

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Detection of circulating tumor cells in bladder cancer patients

Cited by 34 publications

References 104 publications

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

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