TEST:

CELLSEARCH®

In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

The results from the CECinVOD study collectively confirm the endothelial injury in allo-HCT and in SOS/VOD development, suggesting CECs as a valuable biomarker for its diagnosis and for the identification of patients at higher risk of this complication, especially in cases of late-onset SOS/VOD. Furthermore, CEC kinetics may assist in treatment strategies by providing insights into the optimal timing for discontinuing defibrotide treatment.

This work provides proof of principle of the power of this approach and paves the way for a validation study aimed at evaluating early ctDNA-guided treatment decisions in stage IV melanoma. The NGS-based molecular profile complemented the analysis of ctDNA trend and, together with CMC analysis, revealed to be useful in capturing tumor evolution.

P1, N=90, Recruiting, Emory University | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Jun 2026

P=N/A, N=65, Recruiting, Menarini Silicon Biosystems, INC | Trial primary completion date: Mar 2024 --> Dec 2024

P3; N=4994; Active, not recruiting; Sponsor:National Cancer Institute (NCI)

Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries.

Integrating CellSearch, DEPArray, and low-pass sequencing provides a minimally-invasive approach to compare genomic characteristics in DLL3-positive and negative CTCs from SCLC patients. Extension of this approach to a larger patient cohort and employing machine learning algorithms will facilitate identification of patterns within diverse CNA profiles, improving patient stratification and predicting treatment responses for personalized therapeutic strategies in SCLC.

Label-free acoustophoresis is a potential method for future non-invasive molecular interrogation of metastatic cancers. We believe Acoustophoresis is a promising technology for CTC enrichment with the possibility to detect new subclasses of CTCs as well as cell clusters not detectable with CellSearch. CTC-clusters has previously been proposed as a promising and potent predictor to monitor progressive disease and is associated with earlier onset of metastatic disease and poor prognosis, which makes acoustophoresis ability to identify clusters of high interest.

These findings emphasize that ILC is a distinct entity also in the liquid biopsy features. Because of the low prevalence of ILC, research efforts should be directed at combining data from ILC pts to better characterize this subtype of BC and understand the reason behind the different associations with OS as compared to IDC.

Automated identification and enumeration of CTCs in CELLSEARCH images with CellFind can remove human subjectivity from the review process and maximize standardization among different research centers. CellFind performed better than most operators and reduced the data processing time required for each blood sample by the operator.

In summary, the novel scIMPACT workflow enabled reliable and accurate genomic profiling of patient-derived CTCs in late-stage breast cancer patients. Our proof-of-concept study revealed evidence of genetic diversity of SNVs among the examined CTCs, which might have been acquired late in progression but relevant for therapy escape in the studied cases. Further analyses are still needed for assessing the generalizability of our finding as well as for deeper understanding of the molecular basis orchestrating the establishment and maintenance of heterogeneous genotypes of CTCs in breast cancer.

The PACE study (NCT03147287) enrolled patients (pts) with hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) MBC after progression on CDK4/6 inhibitor (CDK4/6i) and endocrine therapy, and randomized pts to fulvestrant (ful) alone; ful with palbociclib; or ful, palbociclib, and avelumab [Mayer et al., SABCS 2022]. Future analyses are needed to investigate the correlation between ER expression levels on CTCs with survival and treatment response. This, together with information about the mutational status of ESR1 by ctDNA sequencing, might provide a new perspective on the development of resistance to ful and CDK4/6i in HR+/HER2- MBC.

In this proof-of-concept study we show that a liquid biopsy-based approach for single cell analysis from CSF holds potential for innovative diagnostic assays for patients with suspected LM. Combining CTC quantification with molecular single cell analysis could enable us to define predictive tests to select novel treatment options for patients with LM in the future.

DPcells can have an aberrant genome, supporting their malignancy. Contrary to CTCs, DPcells' CNA profiles are not clonal and, in vivo, they can only be observed in immunocompetent models; both observations support the tumor/immune fusion hypothesis. Finally, DPcells show metastatic potential in mice, in line with the association with worse survival we previously observed in BC pts.

HER2+ CTCs were also detected in tissue HER2- patients, indicating further investigations are warranted into the clinical significance of HER2+ CTCs. High CTC counts were associated with an increase in PLR, NLR and PAI-1 levels indicating that high CTC trafficking in MBC is associated with an altered inflammatory response which may aid in metastatic dissemination.

In neoadjvuantly treated patients, there was no significant difference in CTC counts in the ILC group versus the IDC group (mean 0.89 CTCs/mL versus 1.06 CTCs/mL respectively, p = 0.82). Our findings contribute to the limited literature on CTCs and DTCs in ILC, and suggest that clinical utility and optimal thresholds for CTC and DTC assays may differ by histologic subtype in early-stage breast cancer.

Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumor surrogate material – although they may be prognostically less relevant than EpCAM high-expressing CTCs – and have particular benefit if no CTCs are detected using EpCAM dependent technologies.

Many adhesion proteins and stemness drivers as glycoprotein substrates of ST6GAL1 drive CTC clustering and metastatic seeding. Neutralizing antibodies against these clustering drivers inhibit CTC cluster formation and improve therapy response, thereby blocking lung metastasis in TNBC.

P=N/A; Not yet recruiting --> Recruiting

Studies have found that CTC numbers are predictive of bone metastasis in breast, prostate and lung cancer. Further work is required to incorporate information on CTCs into current staging systems to guide treatment in the prevention of tumour progression into bone.

Among 189 patients (25.0%) with ET recommended by clinicians and high CTC count, chemotherapy was superior to ET (HR for death, 0.53; 95% CI, 0.36 to 0.78; P = .001). In case of a discordant estimate, OS data demonstrate the clinical utility of CTC count.

P=N/A; Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.

P3 | N=800 | NCT01710605 | "...the STIC CTC trial demonstrates that the use of CTC count as a tool for choosing between endocrine therapy (ET) and chemotherapy (CT) is non-inferior to the investigator's choice in terms of short and long-term clinical outcomes. While approximately 60% of the study participants had a concordant indication between the clinical risk-guided arm and the CTC-guided treatment arm, in the subgroup of patients with a discordant estimate, the use of frontline CT in the CTC-guided treatment arm instead of ET yielded a clinically and statistically significant gain of 16.4 months in median overall survival (OS)."

As such, CTCs represent a target of utmost importance in cancer research and therapy. In this chapter, we describe a workflow for the enrichment of CTCs with the FDA-cleared CellSearch system followed by the isolation of single CTCs using the DEPArrayâ„¢ technology enabling further molecular single-cell analyses.

P3 | N= 105 | DETECT III (NCT01619111) | "A total of 2,137 patients with HER2 negative MBC were screened for HER2 positive CTCs using Menarini Silicon Biosystems' CELLSEARCH^® CTC System and the CELLSEARCH HER2 tumor phenotyping reagent. 105 patients, with at least one detected HER2 positive CTC in the initial CTC screening phase, were randomized to either lapatinib in combination with standard therapy or to standard therapy alone. Patients in the lapatinib arm had a significantly improved OS with a median survival time of 20.5 months compared to a median survival time of 9.1 months for patients in the standard arm (HR 0.54; 95% CI 0.34–0.86; p = 0.008)...the results indicate that CTC-guided treatment allocation may help optimize treatment strategies and should therefore be further investigated. The study also confirmed the prognostic role of CELLSEARCH CTC enumeration."

CTC frequency is a strong, independent predictor of survival in patients with CUP. CTC quantification provides a useful prognostic tool in the management of these patients.

This newly established AXL CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti-AXL therapies.

The number of CTCs detected in 2% aliquots of DLA using FETCH was unchanged compared to CellSearch and did not decrease when using down to 10% of the volume of immunomagnetic anti-EpCAM ferrofluids normally used in a CellSearch test, whereas the number of co-enriched white blood cells reduced a median 3.2-fold. Processing of a 20% aliquot of DLA with FETCH resulted in a 14-fold increase in CTCs compared to the processing of 2% aliquots of DLA using CellSearch and a total 42-fold median increase in CTCs compared to peripheral-blood CellSearch.

CTC count and AS of cfDNA at baseline and during treatment predict clinical response to radium-223 in patients with mCRPC, warranting future evaluation of their value in treatment guidance.

Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.

This workflow enables the enrichment, detection, and isolation of single CTCs for individual transcriptome analyses. The discrimination of apoptotic and non-apoptotic cells allows to focus on CTCs with a high RNA integrity to ensure a successful transcriptome analysis.

Pts receiving TBI-based regimen were more likely to develop VOD compared to those receiving Treosulfan (10 to 14 g/m2) or Busulfan ev (9...After defibrotide treatment, the CEC levels increased in the first week, while they progressively decreased during the VOD treatment (T6 and T7, -50,7% and -71,5%, respectively)...We show that CECs can be considered reliable marker of endothelial damage in alloSCT pts, highlighting the impact of previous treatments, the conditioning regimen, and allo-SCT itself. Increased CEC level may be helpful to confirm VOD diagnosis, as well as their monitoring may be useful to evaluate the response to the treatment for VOD.

In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones. In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC.

The capture rate and specificity of OmiCell® System are 97.2% and 90%, respectively, and the limitation of detection is 1 CTC per 5 ml blood. In the cohort, we detected ≥ 1 CTCs in 59 out of 65 samples at baseline (90.8%, range: 1–55 CTCs, median = 6). Two to four months after baseline, we detected ≥ 1 CTCs in 34 out of 40 samples (85%, range: 1–58 CTCs, median = 6).

Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

P=N/A; Initiation date: Sep 2023 --> Dec 2023

Among 189 patients (25.0%) with ET recommended by clinicians and high CTC count, chemotherapy was superior to ET (HR for death, 0.53; 95% CI, 0.36 to 0.78; P = .001). In case of a discordant estimate, OS data demonstrate the clinical utility of CTC count.

We conclude that DLA was unable to increase the detection rate of CTCs in hormone receptor positive, HER2 negative patients with early breast cancer being on treatment for a median duration of 5 years. Additional circulating tumor DNA analyses are planned.

The combined presence of CTCs and elevated cfDNA concentrations in patients with stage III/IV IBC after completion of neoadjuvant chemotherapy was associated with disease relapse regardless of pCR status. A combination of elevated cfDNA and CTC detection signatures after completion of neoadjuvant chemotherapy may be useful for risk stratification and adjuvant systemic therapy planning.

Detection of tdEVs was associated with particular genomic profiles. These alterations seem to be different in IBC further underlying a different biology of this BC subtype. Additional studies are needed to explore how to integrate different liquid-biopsy based biomarkers in the management of pts with MBC.

Our upcoming trial, RAMP UP (NCT05344833), investigates the safety and efficacy of isatuximab combined with lenalidomide as a maintenance regimen in patients who are MRD-positive after autologous transplant. One patient has been enrolled, and two have signed informed consent for enrollment. Ultimately, our study aims to inform MRD risk-adapted approaches for maintenance therapy in myeloma.