Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer

Sotelo, Miguel; Sastre, Javier; Maestro, M.L.; Veganzones, Silvia; Vieitez, José María; Alonso, Vicente; Grávalos, Cristina; Escudero, P.; Vera, Ruth; Aranda, Enrique; García‐Alfonso, Pilar; Gallego-Plazas, Javier; López, Carlos; Pericay, Carles; Arriví, A.; Vicente, Pilar; Ballesteros, P.; Élez, Elena; López‐Ladrón, Amelia; Dı́az-Rubio, Eduardo

doi:10.1093/annonc/mdu568

Cited by 64 publications

(46 citation statements)

References 17 publications

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“…In addition, patients with detectable CTC have a significantly higher risk to develop a recurrent disease. Interestingly, the detection of CTC did not correlate with lymph node metastases, which is in line with previous reports [19, 36]. Furthermore, in our study population we were not able to prove a prognostic influence of detectable CTC or DTC in early stage (UICC stage II) patients.…”

Section: Discussionsupporting

confidence: 90%

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

et al. 2017

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BackgroundDetection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far.MethodsIn this prospective monocentric study 299 patients with colon cancer were included. CTC and DTC were detected using CK20 RT-PCR as well as immunocytochemistry staining with anti-pan-keratin and anti-EpCAM antibodies. The primary endpoints were: Evaluation of CTC and DTC at the time of surgery and correlation with main tumor characteristics and overall (OS) and disease free survival (DFS).ResultsPatients with detectable CTC had a 5-year OS rate of 68% compared to a 5-year OS rate of 85% in patients without detectable CTC in the blood (p = 0.002). Detection of DTC in the bone marrow with CK20 RT-PCR was not associated with a worse OS or DFS. Detection of pan-cytokeratin positive DTC in the bone marrow correlated with a significantly reduced 5-year OS rate (p = 0.048), but detection of DTC in the bone marrow with the anti-EpCAM antibody did not significantly influence the 5-year OS rate (p = 0.958). By multivariate analyses only detection of CTC with CK20 RT-PCR in the blood was revealed to be an independent predictor of worse OS (HR1.94; 95% CI 1.0–3.7; p = 0.04) and DFS (HR 1.94; 95% CI 1.1–3.7; p = 0.044).ConclusionsDetection of CTC with CK20 RT-PCR is a highly specific and independent prognostic marker in colon cancer patients. Detection of DTC in the bone marrow with CK20 RT-PCR or immunohistochemistry with anti-EpCAM antibody is not associated with a negative prognostic influence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3035-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

et al. 2017

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“…Furthermore, some large‐scale meta‐analyses have shown the prognostic significance of CTCs detected using the CellSearch system in metastatic breast cancer or CRC (Bidard et al., 2014; Lv et al., 2015; Huang et al., 2014). In contrast, a recent large study using this system showed that there was no prognostic significance of CTCs in CRC (Sotelo et al., 2015). Pantel et al.…”

Section: Markers Of Ctcs In the Pb Or Bm And Clinical Significance Ofmentioning

confidence: 87%

“…Furthermore, some large-scale meta-analyses have shown the prognostic significance of CTCs detected using the CellSearch system in metastatic breast cancer or CRC Lv et al, 2015;Huang et al, 2014). In contrast, a recent large study using this system showed that there was no prognostic significance of CTCs in CRC (Sotelo et al, 2015). Pantel et al (2012) reported that the CellSearch system gave false-positive results in patients with benign colorectal diseases, such as inflammatory colon diseases, and demonstrated that further molecular characterization of circulating epithelial cells was needed for the use of this CTC testing modality (Pantel et al, 2012).…”

Section: ) Immunocytologymentioning

confidence: 99%

Clinical and biological significance of circulating tumor cells in cancer

et al. 2016

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Initially, epithelial markers, such as EpCAM and cytokeratins (CKs), identified using immunocytochemistry or reverse transcription polymerase chain reaction (RT-PCR) were used to identify CTCs in PB or BM. Recently, however, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes also have been examined to facilitate detection of CTCs with metastatic potential. Moreover, the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTC markers owing to their roles in the biological progression of metastasis. In addition to these markers, researchers have attempted to develop detection or capture techniques for CTCs. Notably, however, the establishment of metastasis requires cancer-host interactions. Markers from host cells, such as macrophages, mesenchymal stem cells, and bone marrow-derived cells, which constitute the premetastatic niche, may become novel biomarkers for predicting relapse or metastasis or monitoring the effects of treatment. Biological studies of CTCs are still emerging. However, recent technical innovations, such as next-generation sequencing, are being used more commonly and could help to clarify the mechanism of metastasis. Additionally, biological findings are gradually being accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells.

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“…CTCs comprise a low percentage of circulating cells commonly present in cancer patients. With numbers as low as one CTC per 10 6 −10 7 peripheral blood leukocytes, enrichment, investigation, and quantification of CTCs has proven extremely difficult [5], but the effort has been validated by current studies showing that the presence of CTCs in peripheral blood is a valuable prognostic marker in cancer patients [6, 7, 8, 9, 10, 11, 12], and an useful predictor of progression-free and overall survival. Results from clinical studies have shown breast, prostate and colorectal cancer patients with fewer CTCs in their peripheral blood survived longer than those with more CTCs [7, 8, 13].…”

Section: Introductionmentioning

confidence: 99%

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

et al. 2016

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Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5–87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59–100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.

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Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer

Abstract: CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.

Cited by 64 publications

References 17 publications

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

Clinical and biological significance of circulating tumor cells in cancer

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

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