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CELLSEARCH®

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. 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.

No abstract available

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 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.

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.

4. Bidard, JCO 2023.

29 (58%) with prior >2 ARPI, 29 (58%) with >1 chemo, 14 (28%) with Ra-223, 2 (4%) with 177 Lu-J591... A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most had PSA decline with favorable PFS and OS compared to historical controls and similar to PSMA-selected targeted radionuclide studies administering multiple cycles in a less dose-intense approach.

A high proportion of IBC patients who achieved pCR had MRD, as demonstrated by persistent CTCs. CTCs portended worse prognosis in patients with IBC, even after pCR. Future incorporation of longitudinal CTC monitoring may be helpful in identifying patients at risk for relapse despite having achieved a pCR.

CTC reduction at Week 9 and 17 proved prognostic of improved rPFS in both treatment arms in TALAPRO-2. To our knowledge, this is the first time such an association has been demonstrated in a phase 3 trial featuring a PARP inhibitor. Not all regions supported CTC collection, and missing results mainly reflected technical and logistical limitations.

Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.

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; Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Jun 2026

P=N/A; 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.