TEST:

CELLSEARCH®

The comprehensive multivariate Cox regression analysis underscored the independent prognostic impact of CTC presence (HR=1.274; 95% CI, 1.119-1.451; P<0.001) and the implementation of non-surgical treatment (HR=0.268; 95% CI, 0.119-0.607; P=0.002) on the prognosis of individuals grappling with HNC. In conclusion, the levels of CTCs were an independent factor affecting outcomes in patients with HNC, with CTC-positive patients showing significantly shorter survival compared with CTC-negative cases.

We conducted a comprehensive analysis of the tumor properties, radiological features, and genomic characteristics that are significantly associated with CTCs in different lung cancer subtypes. This study helps elucidate the formation mechanism and relevant major regulation molecules of CTCs.

In this review, we discuss the clinical applications of CTCs, current status of research, and efforts to incorporate CTC analysis into clinical practice. Additionally, we discuss potential challenges and future directions for integrating CTC analysis into clinical practice.

P=N/A, N=65, Recruiting, Menarini Silicon Biosystems, INC | Trial completion date: Dec 2024 --> Aug 2026

P=N/A, N=180, Not yet recruiting, Cytoastra | Trial completion date: Jul 2025 --> Nov 2025 | Initiation date: Sep 2024 --> Jan 2025 | Trial primary completion date: Jul 2025 --> Nov 2025

The count of CTCs has been established as a predictive marker in terms of clinically important parameters namely progression-free survival (PFS) and overall survival (OS). The CTC-count value was significantly correlated with PFS and OS rates.

Using the epithelial MCF-7 and mesenchymal Hela cells as models, the ECL cytosensor demonstrates excellent performance in identifying cells spiked into whole blood. This study presents a novel approach for early detection of metastasis, tracking tumor recurrence, and monitoring therapeutic efficacy.

Currently, two BCMA-targeting BsAbs (teclistamab and elranatamab) and one GPRC5D-targeting BsAb (talquetamab) have regulatory approval for the treatment of patients (pts) with RRMM. Conclusions : CMMC counts through serial peripheral blood sampling can be used to assess disease burden and early kinetics of response to BsAb therapy. Further follow-up and additional cohorts are planned to confirm performance of this assay as a biomarker in predicting response and long-term outcomes in patients receiving BsAb and other therapies, as well as interrogating mechanisms of resistance through targeted sequencing and analysis of tumor-associated antigens of enumerated cells.

To develop a robust assay, ongoing clinical experiments aim to quantify cell loss during sample preparation and validate performance with patient samples at different stages of MM. Beyond CPCs, our models show promise in detecting and isolating other rare cell types, including circulating solid tumor cells and stem cells from breast milk and amniotic fluid, establishing them as valuable tools in rare-cell biology.

It is possible to identify and quantify HER2 expression on CTCs. HER2+ CTCs were detected in a high percentage of patients regardless of their HER2 status on tissue, indicating high intra-patient heterogeneity. HER2+ BC cohort exhibited a significantly higher proportion of HER2+ CTCs compared to the HER2- BC cohort.

Further studies including a larger number of pts are needed to validate and better elucidate these findings. The study of CTCCL could shed light on the distinct pattern of metastatic spread of ILC, potentially offering therapeutic opportunities, and serving as a useful prognostic factor.

The current study showed the feasibility of a real-time HER2 assessment on CTCs enriched from mBC pts. The developed pipeline was able to count and identify HER2-positive CTCs with higher efficiency than the gold-standard CellSearch® overall and interestingly, also in the HER2-negative subgroup. This is a preliminary analysis that should be confirmed in larger cohorts.

Private mutations in resistance related genes and tumor driver genes could impact drug susceptibility and therapy resistance. Therefore, the CSF-based liquid biopsy should be considered for genetic profiling of LMs, potentially improving diagnosis, treatment monitoring, and targeted therapy selection.

Linearity testing, where the cell lines were spiked in 7.5mL blood, showed high levels of reproducibility across the clinical range (1000 cells to 0) with an R2 = 0.99. The CELLSEARCH® CTC-HER2 Low test meets a critical clinical need that breast cancer patients, positive or classified as negative from a tissue biopsy, in need of a current evaluation of their metastatic breast cancer HER2 status, through any line of treatment, can do so from one blood draw using a test that can detect HER2 expression to very low levels.

Conclusions The ACT-MBC analyses to date show that assessing CTCs along with standard modalities enhanced the ability of physicians to assess treatment response, guide treatment decisions and may additionally alter the timing of restaging scans. In summary, these data suggest that assessment of CTCs may provide an important tool for clinical treatment decision making.

The study has explored the potential prognostic values of CTCs, immune cells, and CTC immune cell interactions by correlating their presence, abundance, and spatial information, with clinical outcomes. These outcomes may include patient survival, disease progression, and treatment response. By combining multidimensional data derived from cell morphology, biomarker expression, and spatial relationships, we aim to develop predictive models capable of stratifying patients into unique risk groups.

We will ask whether the mutational or the functional assays allow predicting the clinical response of the patient and provide a novel rational that could support decision making of the molecular tumor board. The results will be presented on the poster.

Lower PreRX CTCs predicted for improved PFS after ablation using the HDSCA assay. The pre-specified CTC analyses provide consistent results using two independent assays highlighting the robustness of the finding. These hypothesis-generating findings suggest that PFS is improved in CTC negative OMBC patients who are treated with ablation.

Among stage III IBC patients with relapse, MRD was detected with a median lead time of approximately 6 months prior to radiographic confirmation of disease recurrence. Incorporation of serial assessments of MRD may offer the opportunity for early systemic treatment intervention in IBC patients with high risk of relapse.

Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

The developed novel multi-marker liquid bead array assay for the simultaneous detection of PIK3CA and ESR1 hotspot mutations in single CTCs is highly specific, highly sensitive, high-throughput, and sample-, cost-, and time-saving. This multi-marker liquid bead array assay can be extended to detect up to 100 mutations in many genes at once and can be applied for bulk CTC and ctDNA analysis.

P=N/A; Trial primary completion date: Sep 2024 --> Sep 2025

When spiked into blood, the average capture efficiencies were 27.7 and 46.8% at concentrations of 10 and 100 µg/ml, respectively. These results suggest that the CSV‑chip is useful for detecting mesenchymal‑type cells and has potential applications in capturing EMT‑CTCs.

The results demonstrated that the combined use of anti-EpCAM antibody and rVAR2 significantly enhanced the capture efficiency to an average of 88.2% compared with 40.6% when using only anti-EpCAM and 56.6% when using only rVAR2. These findings suggest that a dual-marker approach using anti-EpCAM and rVAR2 can provide a more robust and sensitive method for CTC enrichment in NSCLC, potentially leading to better diagnostic and prognostic outcomes.

No pathogenic germline variants were found. Our data support the conclusion that CTCs analysis may be used to identify mutations in patients to identify those more likely to metastasize.

These findings underscore the potential of CTC flow cytometry as a novel diagnostic modality for investigating tumour biology and monitoring disease progression in patients receiving surgical treatment. Especially the assessment of blood from fresh surgical specimens offers access to the compartment of mesenterial blood avoiding additional interventions. It can be used as an adjunct to the conventional histopathological workup in GI cancers.

In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course.

This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy.

Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

A high proportion of HER2-low expressors demonstrated HER2-CTC positivity. Monitoring CTC-HER2 status may offer prognostic value in patients with IBC.

Xaluritamig showed prolonged OS relative to historic benchmarks in heavily pretreated pts with poor prognostic features. CTC enumeration is highly prognostic of OS at baseline, and CTC conversion and PSA declines may predict response from xaluritamig treatment. Further validation is warranted as CTCs may guide future clinical development of xaluritamig by early identifying the treatment benefit in pts.

CTC clearance at the end of study treatment is associated with improved outcome and might be used to assess treatment response.

Although preliminary, integration of diverse circulating biomarkers showed the potential to refine prognosis, inform clinical decisions, and deepen our understanding of the biology of the IBC subtype.

A high proportion of IBC patients had persistent MRD despite achieving pCR. Longitudinal assessment of the molecular landscape is necessary for optimal risk stratification in patients with IBC.

P=N/A; N=3000; Not yet recruiting; Sponsor:Zhejiang University

In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy.

This workflow facilitates the enrichment, detection and isolation of single CTCs for the analysis of transcriptomic profiles. Setting a focus on CTCs with a high RNA integrity by the discrimination of apoptotic and non-apoptotic cells provides a high reliability of the generated RNA sequencing data making them more suitable for scientific research.

Ann Oncol, 2012. 23(3): p. 618-24.

In conclusion, DLA tended to increase the proportion of patients with detectable CTCs but was also associated with low recovery. Both cfDNA and CTCs were correlated with clinical parameters such as LDH levels and extracranial tumor burden.

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.

This study showed a moderate to strong correlation between the 2 technologies for baseline CTCs detection and moderate to poor correlation for CTCs detection after 2 cycles of therapy. No association was found between CTCs and tissue PD-L1 expression. Future work needs to further investigate the role of PD-L1 expression on CTCs.

4. Bidard, JCO 2023.