Perioperative Detection and Characterization of Circulating Tumor Cells in Patients Undergoing Colorectal Cancer Liver and Lung Metastasectomy
More sensitive techniques to detect occult disease are needed for metastatic CRC (mCRC)
patients, and perioperative analysis of circulating tumor cells (CTCs) may provide an
outstanding opportunity to develop such innovative methods.
Determine kinetics of CTC shedding into the circulation: Perioperative CTC detection has the
potential to explain how and when CTCs are shed into the blood. Findings could explain the
nature of CTCs with important impact on understanding metastatic spread and relevant
Since this protocol includes blood draws at multiple time points at different distances from
the metastases, results could further clarify if the rarity or absence of CTCs in the
peripheral blood of some mCRC patients can be explained by dilution. Comparison of patients
with CRC liver to lung metastases might help explain different patterns of organ spread.
Results of this study could establish CTCs as a prognostic biomarker identifying candidates
who will benefit from metastasectomy or for those who are candidates for additional or
palliative systemic treatments because of a high risk for later recurrence.
- Develop effective system for isolation, enumeration, enrichment and further
characterization of live CTCs: One of the current issues of CTC analysis is the
enrichment of those rare cells from blood. We plan to analyze perioperatively drawn
blood using the flexible micro spring array (FMSA) device. The FMSA mitigates the
stresses experienced by CTCs during their isolation from blood and enables viable
capture. The geometric design and filtration pressures have been optimized to maximize
capture efficiency, enrichment against leukocytes, and tumor cell viability. Peripheral
blood as well as blood from the direct tumor environment (taken from the OR suctioning
system) will be analyzed to compare the sensitivity of the FMSA and CellSearch device.
Since the FMSA allows for isolation of live CTCs, they will be processed for further
single cell characterization.
- Find characteristics of different CTC populations: We hypothesize that CTCs will be
enriched for cancer stem cell markers as well as markers for poor prognosis and
aggressive tumor growth. Our novel approach to screen and quantify a panel of
biomarkers simultaneously with analysis of the CTC markers utilized by the CellSearch
system to analyze of CTCs is unique. We view our assays as potential "liquid biopsies"
that can screen for markers of prognosis, sensitivity to chemotherapy, response to
therapy, as well as for proteins involved in proliferation, apoptosis, and immune
Furthermore, we plan to perform single cell analysis of gene mutations and gene expression.
Next generation genomic sequencing of single CTCs may allow us to determine a genetic
signature for colorectal CTCs and to identify novel biomarkers for CTC detection, disease
monitoring, and therapeutic efficacy. Furthermore, the extent of heterogeneity among
initially isolated CTCs, which can be compared to the primary tumor and CTCs growing in
vitro, will be studied. Single CTC analysis has the potential to identify novel gene and
signal transduction pathways that are activated in CTCs and to compare this genomic profile
to that of the primary tumor and patient metastasis. Single cell genomic analysis in CTCs is
highly innovative and will provide important information for disease monitoring as well as
shed light on the underlying biology of CTCs.
Observational Model: Cohort, Time Perspective: Prospective
Quantity of CTCs isolated during liver and/or lung metastasectomy
Define in which quantity CTCs are retrievable from different blood compartments and lost blood during CRC liver and lung metastases surgery using the Veridex CellSearch system and FMSA filter device
Jussuf T Kaifi, MD PhD
MS Hershey Medical Center
United States: Institutional Review Board
|MS Hershey Medical Center||Hershey, Pennsylvania 17033|