scholarly journals Isolation and Enumeration of Circulating Tumor Cells (CTC) as Prognostic and Predictive Biomarkers in Post-Operative m-CRC

2021 ◽  
pp. 1-6
Author(s):  
Swaroop G

Circulating Tumor Cells (CTCs) presents non-invasive, repeatable investigation of patient‘s disease. In metastatic Colorectal Cancer (m-CRC) patients, CTC enumerations have been comprehensively studied in evaluating metastatic disease. CTC analysis has been shifting from enumeration to more sophisticated molecular depiction of tumor cells, which is used for liquid biopsy of the tumor, reflecting cytological and molecular changes in metastatic patients over time. In this study, CTC enumeration in advanced and localized metastatic colorectal cancer, highlights the vital gains as well as the challenges posed by various approaches, and their implications for advancing disease management. Detection of circulating tumor cells (CTC‘s) or circulating free tumor DNA (ctDNA) to conduct chemotherapy and reporting prognosis is extremely important, In view of the detail CTC has the potential to offer multiple samples by way of sequential minimally-invasive liquid biopsies. In fastidious, there is escalating evidence for the efficacy of CTC‘s in the clinical management of metastatic colorectal cancer (CRC). With most studies confirming the association of elevated CTC counts with worse prognosis. CTC‘s were first identified by Ashworth in 1869. CTC research has been vulnerable by the failure to constantly detect these typical cells. While the normal range of WBCs in human blood is 4.5-119/L, there may only be a few CTC‘s. The most widely used CTC enumeration platform, Cell-Search (Veridex LLC, NJ, USA) was approved for clinical use. As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. Investigations were carried out that Circulating Tumor Cells (CTCs) could predict clinical prognosis in patients with mCRC. This pilot study, demonstrates that CTCs can serve as both prognostic and predictive factor for patients with mCRC. The presence of at least three CTCs at baseline and follow-up is a strong independent prognostic factor for inferior PFS and OS. When utilized in combination with imaging studies, CTCs provide additional prognostic information. There are several studies for which CTCs could have efficacy inmetastatic colorectal cancer. The statistics suggests that CTCs may be used as a stratification feature in metastatic disease treatment trials. The current list of validated prognostic factors is short, with only routine status being universally recognized. Further study should prospectively deal with modification of regimens based on unfavorable CTCs early in the course of treatment will result in enhancement in PFS or OS. As treatment has become more effective for metastatic disease, decision making has become more complicated. Five classes of drugs are on hand for treatment. The most common initial chemotherapy is a fluoropyrimidine with oxaliplatin or irinotecan. CTC levels drawn at 3 to 5 weeks and 6 to 12 weeks, before PET imaging, may lead to prospective regimen choices and standby patients from unnecessary drug toxicity by suggesting that an early change in treatment is defensible.

2008 ◽  
Vol 26 (19) ◽  
pp. 3213-3221 ◽  
Author(s):  
Steven J. Cohen ◽  
Cornelis J.A. Punt ◽  
Nicholas Iannotti ◽  
Bruce H. Saidman ◽  
Kert D. Sabbath ◽  
...  

PurposeAs treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and MethodsIn a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.ResultsPatients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.ConclusionThe number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.


BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Yuurin Kondo ◽  
Kazuhiko Hayashi ◽  
Kazuyuki Kawakami ◽  
Yukari Miwa ◽  
Hiroshi Hayashi ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40476 ◽  
Author(s):  
Jorge Barbazán ◽  
Lorena Alonso-Alconada ◽  
Laura Muinelo-Romay ◽  
María Vieito ◽  
Alicia Abalo ◽  
...  

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 239-239
Author(s):  
Jeanny B. Aragon-Ching ◽  
Samuel J. Simmens ◽  
Steven R. Patierno ◽  
Robert S. Siegel

239 Background: Staging for BR is challenging since the yield of computed tomography (CT) and bone scans are low, especially in patients with low prostate specific antigens (PSA) levels. We examined the utility of circulating tumor cells (CTCs) to predict metastatic disease in a cohort of patients who presented with BR (Aragon-Ching, et. al. ASCO GU 2011;abstr 60). Methods: 33 pts enrolled from May 2010 to September 2011 with BR, defined as patients (pts) who have undergone primary treatment with PSA rise to >/= 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy, were included. PSA doubling time (PSADT), scan results, Gleason scores, age, testosterone levels were all obtained. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. BR patients with equivocal CT and/or bone scan results who were biopsiable and consentable underwent bone biopsy to confirm metastatic disease. Results: The median age for 33 patients was 71 y/o (range: 51 – 91), median PSA of 1.7 ng/mL (range 0.2 – 65.8), testosterone levels of 315.5 ng/dL (range: 31 – 727), Gleason score of 7, hemoglobin of 13.78 g/dL, BMI of 27.72 and alkaline phosphatase of 68 IU/L. Prostatectomy was the primary treatment in 23 pts, radiotherapy in 9 pts and Cyberknife in 1 pt. Median PSADT varied between 0.35 to 55.2 months. Only a small number of patients had either biopsy confirmed metastatic disease (n=2) or detectable CTC (n=3). Both of the 2 patients with metastatic disease had detectable CTC (sensitivity = 1.00, 95% CI: .34, 1.00). For the patients without signs or confirmation of metastatic disease, 30/31 had no detectable CTC (specificity = .97, 95% CI: .84, .99). Conclusions: While most pts with BR have negative blood CTCs, patients with detectable CTCs and equivocal findings on scans should raise suspicion and prompt a search for metastatic disease, given increasing available treatment options for metastatic prostate cancer. However, the limited number of patients may preclude reliable statistical evaluation of CTCs in this population. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14753-e14753
Author(s):  
Stephanie Shishido ◽  
Peter Kuhn

e14753 Background: The liquid biopsy is a noninvasive route to evaluate circulating tumor cells (CTCs) during the course of treatment to gain understanding of tumor biology, with potential prognostic utility. CTCs could serve as a predictive biomarker while aiding in the identification of resistance mechanisms to treatment through single cell genomic and proteomic analysis providing a longitudinal snapshots of tumor heterogeneity. Methods: Through the use of the high definition single cell assay (HD-SCA) workflow, we characterized the rare circulating cells to determine prognostic value of the liquid biopsy in monitoring the efficacy of andecaliximab in a combinational treatment as 1st or 2nd line therapy in patients with metastatic colorectal cancer (mCRC). 174 samples from 95 patients were analyzed to determine the significance of CTCs during treatment. Results: HD-CTCs were detected in 31% of samples, with 41 (43%) patients being CTC positive in at least 1 timepoint during the study. Patients receiving 1st line therapy presented with a median of 0 (range 0-346.04) and a mean of 9.49 (±14.06) HD-CTC/mL at baseline (BL). At initiation of 2nd line therapy, patients presented with a median of 0 HD-CTC/mL (range 0-277.37) and a mean of 10.94 (±15.32). There was no association between BL HD-CTC/mL and response, but for the 20 patients with > 1 HD-CTC at BL, there was a trend toward response for higher HD-CTC/mL (non-response: mean 2.8, n = 12; response: mean 89.7, n = 8; p = .04). The 3 patients with > 10 HD-CTC/mL at BL had undetectable HD-CTC on-treatment, which accompanied radiologic partial response; however, the 2 patients with complete radiological response had no HD-CTC detected at BL. In case studies, treatment pressure led to an observable change in HD-CTC morphology and genomic instability (single cell CNV analysis), suggesting these parameters may inform prognosis. Conclusions: Characterization of CTCs from patients with mCRC is feasible and may provide prognostic information to guide clinical decision making. Further evaluation of CTCs for pharmacodynamics and clinical monitoring in patients with mCRC is warranted.


2011 ◽  
Vol 102 (6) ◽  
pp. 1188-1192 ◽  
Author(s):  
Satoshi Matsusaka ◽  
Mitsukuni Suenaga ◽  
Yuji Mishima ◽  
Ryoko Kuniyoshi ◽  
Koichi Takagi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document