Survey Results Q1. How would you best describe your organization? Q2. How high would you rate the priority of Circulating Tumor Cells in you organization?
Q3. What do you think is the biggest challenge in current CTC research? A selection of the best responses Technology / Capture Techniques - High performance and high reliability isolation platform - Integrated technologies - Further validated CTC systems for different cancer types, like NSCLC (where Cell Search fail) - Robustness of methodologies - Improving identification and enrichment - I think that establishment and standardization of measurement method is important - Sensitivity of Technology - Sample isolation and characterization - Sensitivity(only between 60-80% of metastasis patients is CTC positive) - Different technologies producing vastly different numbers of cells - Viable cell recovery for downstream analysis - Standardize CTC identification - Reliable platform to detect intact CTC - Recovering the CTCs from the platform/instrument and passing them off to a downstream molecular assay with high efficiency - Always needing to compare with the Gold standard (Veridex) when in fact it is commonly accepted that it is not the right standard for CTC characterisation: how then do you compare technologies that do not share the same objectives? - Multitude of technology platforms vis a vis specific scientific/medical decision-related expectations, and an uniformity of clear understanding of the above by different parties to assure a meaningful exchange of information and experience - Robust detection - Convincing identification (monitoring) - Adequate capture of cells with good membrane integrity in order to do proper molecular analysis - Validation of assay procedures and data; stability of CTCs during transport - Labelling - Isolating a pure population to further characterize - Isolation of big numbers for subsequent analyses - Isolating viable CTC from blood - Rare numbers of cells captured Samples - Intact CTC isolation from the sample - Patient sample availability - Cancer sample access - Obtaining a high quality sample: high recovery of CTCs and high purity, in a small volume - Getting enough viable CTCs in a sample - Getting enough patients with measurable CTCs - Reproducible high quality of samples
- The rarity of the cells in circulation creates a statistical sampling problem - Blood volume required and sensitivity Molecular Characterisation - Cell characterization Cell selection - The molecular characterization of CTCs - Characterization - Purified cells for sequencing - Metabolites analysis - Biological characterization of CTCs - Characterization of CTCs - Molecular Characterization and Accurate accepted counts Biological Understanding of CTCs - Clear definition of what is a CTC Understanding of role in Metastasis - Seeds of metastasis or not - Find new markers for disseminated disease - To find out which CTCs are important for new cancer development and to track back from CTC to primary tumor Relationship between CTC data and Patient Outcomes - Limited data relating to patient outcomes and tumour tissue which is the target of anti cancer regimes - Lack of utility across all cancer types Implementing in the Clinic - Insufficient number of clinical trials and convincing results to bring CTC into clinical use - Determining clinical utility - Determining the unmet need in oncology that CTC's will specifically answer - To put it in a routine of the hospital and to test it before starting any treatment ( drug resistance genes) - The development of new free labelled technologies to provide CTCs from peripheral blood viable for later biomolecular analysis looking for biomarkers for personalized treatments of cancer - Technologies are great, but they need to demonstrate clinical utility for the detection/characterization of CTCs - Changing mindsets within the clinical community - Proving CTCs have clinical utility across multiple cancer types - Evaluation of clinical utility - Many oncologists have no skills and educational background in technology development - Clinical acceptance
Q4. What do you think is the timeline for CTC s to become an important part of the clinical decision making process? Q5. Which of these technologies currently holds the most promise for improving our ability to study and measure CTCs?
Other technologies mentioned include: - Cell Dx (under development) - MMI CellEctor - RosetteSep - Real-time qpcr - GILUPI nanowire - On-Q-ity - Miltenyi - BioRad digital PCR Q6. What are the clinical applications of detection and characterization of CTCs in cancer patients? A selection of the best responses - CTC detection and characterization can improve the diagnostics, choice of the treatment and prognosis of disease outcome. It is very important that CTC (DTC also) can enhance the efficacy of patient management as well as to start to solve the problem of dormant tumor cells, in particularly through the detection of CTC in persons who are in risk groups - Therapeutic decision and monitoring marker for the cancer patients - Contribution to the process of decision making for selecting anti-cancer agents - These cells are well defined targets for understanding tumour biology and improving cancer treatment. The presence of tumor cells in patient's bone marrow or peripheral blood is an early indicator of metastasis and may signal tumor spread sooner than clinical symptoms appear and imaging results confirm a poor prognosis and finally CTCs could used for individualized cancer treatment - Better patient stratification - Correlation with metastasis and gene profile - In a medium-long term the free labelled techs could provide the possibility of a cleaning process of the blood of cancer patients, similar to the "dialysis" - Tailoring therapy to mutation detection, expression profiling, and pathway analysis - A defined method as, e.g., approved for the enumeration of CTCs by Veridex/CellSearch, may be helpful in early detection of prognostic significance and in treatment-modifying decisions. It is much more complicated which of the available technology platforms might be best suited for specific types/profiles of molecular characterizations and appropriate pharmacodynamic assessments (depending on contexts), and this, as I understand, is an area of intensive ongoing research
Q7. Which Cancer Hospitals are leading the way with CTCs? Q8. How can CTC detection and characterization improve drug development? A selection of the best responses - I believe that there are two MAJOR areas where CTCs (properly defined!) may play a role in drug development: 1) Already applied in certain cancer indications (as above) CTCs enumeration, including a longitudinal assessment of potential therapeutic effects of any given drug/agent in development, thus offering a potential early prognostic and to some extent a response/benefit-predictive insight; and 2) Potential for a longitudinal and repetitious PD assessments as long as the CTCs could serve as a reliable surrogate for events occurring at the tumor tissue level. Incidentally, the evaluation of properly defined CTCs should NOT be considered in isolation, and other surrogate molecular biomarkers should be
considered as potentially complementary, e.g., plasma DNA, tumor-derived exosomes/microvesicles, proteomic profiles, circulating endothelial cells (CECs) and their precursors (CEPs). The idea of CTCs as representing a "liquid tumor biopsy" would have to be validated in multiple cancer indications/settings via a multitude of correlative studies which would assess in parallel molecular perturbations within the CTCs/CECs and other surrogate parameters vs. tumor tissue (including stroma & vascular bed). Of course, the attractive aspect of CTCs relates to the possibility of repetitive assessments in the clinic, something that is largely and practically impossible with regard to the tumor tissue (repeated tumor biopsies over time in the otherwise often very sick patients). - Characterization of CTC can influence the testing of the sensitivity of tumor cells to antitumor drugs, disease outcome prognosis - Genomic level and statistical analysis in the clinical study - We will able to see the changes in targeted markers on CTCs during treatment and screen active drugs early using minimal sample size study - We can directly target on the specific receptor or oncogenes and work for the drug development - Apply CTC detection with companion diagnostics and use target-specific anticancer therapeutics, such as SAMiRNA-based anti-cancer therapeutics - Direct selection of small molecule inhibitors to further develop for targeted therapies - Characterization of mechanisms of response and resistance, early endpoints(fast, reliable), detection of responsive subgroups - CTCs may actually become a target for drug development, as opposed to being a surrogate for the primary tumor - Finding biomarkers that correlate with specific outcome, longitudinal monitoring during clinical trials - Build more effective stratification strategies for clinical trials and ultimately, drug indications - Drug development based on understanding the specific genetic aberration in identified CTC at different disease stages
Q9. What do you think is stopping you from making CTCs your top priority? Q10. In your opinion, what needs to be done to further the use of CTCs both in industry and the clinic? - The appropriate funding, unification of method including both of device for CTC detection and biological markers for CTC. Cooperative clinical investigations to unify the methods and the markers to control clinical relevance. - First and foremost, we need a highly reliable system to isolate these cells. currently, there are systems that are non-standardized, not independently verified, that seem to be yielding highly subjective interpretations of what CTCs can or cannot do in the context fo clinical cancer management. this needs to change. - Consistent and validated method approved by regulatory authorities - Increase collaborations, increase patient sample availability - Greater investment in research - Reducing Cost of CTC technologies
- Improve the way of isolation of CTC in order to increase the amount of RNA or DNA. - More qualified clinical evidence - First, industry must provide solid data about higly sensible detection limit (1 in 6 log) under cooperation with clinical evaluation - Work out hold ups in third party reimbursement - 1 CPT code with reimbursement to cover CellSearch kit costs and tech labor, a minimum of $500.00 Get insurance to cover 1-2 CTC to be used for screening progression of non-metastatic disease to metastatic; It is cheaper than scans - Specalised conference to learn about progress - Demonstrate that CTC can be obtained from a large majority of patients. Determine the relation between tissue status and CTC genetic status. Validate downstream detection methods (PCR, sequencing) for CTC samples. - Decrease the present cost of use. Get intact cells Higher sensitivity and specificity... - Interest and support from industries to collaborate in the development of the new attempts, not only focused on those proceeding from the most famous laboratories and world research centres, but also paying attention in new groups and proposals, i.e, innovating - Combine various available technologies - Results from clinical trials that show the significant benefit of monitoring CTC's need to pile up in order for this to be used more regularly in industry and the clinic. - The use of molecular and gene fingerprints to provide better clinical relevance( not just the garbage of numbers ) and associated gene analysis for the exploitation of currently avaible targeted Rx plus turn the attention of Pharma to frequenty noted or important ampfied genes etc. Each year you have this meeting of the same people telling each other the same things. That's why I neede to see the agenda / program to see if there was anything new or fresh Thank you to those who completed the survey. More information about World CTC can be found at www.ctc-summit.com