Prospective study with circulating tumor cells as potential prognosis biomarker in metastatic colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 203-203 ◽  
Author(s):  
Virgilio Souza E Silva ◽  
Emne Ali Abdallah ◽  
Celso Abdon Lopes de Mello ◽  
Milena Shizue Tariki ◽  
Vinicius Fernando Calsavara ◽  
...  

203 Background: Colorectal cancer (CRC) is one of the most common cancer worldwide. Around 30% present metastatic disease at diagnosis and 50%–60% of patients develop metastasis. New prognostic markers are needed and circulating tumor cells (CTCs) are a promising tool. Methods: Prospective study conducted by blood collection from 75 patients (pts) with metastatic CRC (mCRC), twice, with 2 months interval, together with image exams for therapeutic response evaluation. CTCs were detected by ISET and identified by immunocytochemistry. Results: The mean age was 57.3 years old (24-81). RAS mutations in primary tumor was found in 38% (19/50) of patients (pts) and left colon topography in 41.3% (31/75). Comparing the baseline CTC level (CTC1) with the level at first follow-up (CTC 2), pts with CTC2 – CTC1 > 5.5 per ml demonstrated poor progression-free survival (PFS) (3.2 months) when compared to CTC 2 – CTC1 ≤ 5.5 (9.1 months) (p= 0.005). The median overall survival (OS) was 24.5 months for pts with CTC 1 > 1.5 per ml and 34.2 months for those with CTC1 ≤ 1.5 per (HR=1.89, 95% CI, 1.01 to 3.52; p= 0.041). Patients with RAS mutation (P= 0.001), primary tumor in the right colon (p= 0.014) and expression of Multidrug Resistance Protein 1 in CTCs (p= 0.044) had worse OS. By multivariable analyses, CTC 1 > 1.5/mL (p= 0.025) was an independent prognostic factor. Conclusions: This prospective study confirmed that counts of CTCs at baseline (CTC1) is an important prognostic marker for monitoring mCRC and correlates with other established prognostic factors. Clinical trial information: NCT02979470.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 486-486 ◽  
Author(s):  
Satoshi Matsusaka ◽  
Mitsukuni Suenaga ◽  
Yuji Mishima ◽  
Yasuhito Terui ◽  
Eiji Shinozaki ◽  
...  

486 Background: The purpose of this study was to investigate the potential of circulating tumor cells (CTCs) as a surrogate marker of clinical outcome in metastatic colorectal cancer (mCRC) patients in order to identify Japanese patients responsive to oxaliplatin-based chemotherapy. Methods: The treatment regimen was oxaliplatin-based chemotherapy. Collection of CTCs from whole blood was performed at baseline and at 2 and 8-12 weeks after initiation of chemotherapy. Isolation and enumeration of CTCs was performed using immunomagnetics. Results: Between January 2007 and April 2008, 64 patients with mCRC were enrolled in this prospective study.Patients with ≥3 CTCs at baseline and at 2 and 8-12 weeks had a shorter median progression-free survival (8.5, 7.3, and 1.9 months, respectively) than those with <3 CTCs (9.7, 10.4 and 9.1 months, respectively) (log-rank test: p=0.047, p<0.001, and p<0.001, respectively). Patients with ≥3 CTCs at 2 and 8-12 weeks had a shorter median overall survival (10.2 and 4.1 months, respectively) than those with <3 CTCs (29.1 and 29.1 months, respectively) (p<0.001 and p=0.001, respectively). A spurious early rise in CEA level was observed in 11 patients showing a partial response. On the other hand, no rise in early CTC level was observed among responders. Conclusions: The clinical utility of CTC enumeration in improving our ability to accurately assess treatment benefit and in expediting the identification of effective treatment regimens for individual Japanese patients.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2966
Author(s):  
Thibault Mazard ◽  
Laure Cayrefourcq ◽  
Françoise Perriard ◽  
Hélène Senellart ◽  
Benjamin Linot ◽  
...  

Background: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). Methods: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI–bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan–Meier method and log-rank test. Results: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. Conclusion: CTC detection at D28 and the D0–D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 440-440
Author(s):  
Yoshihito Ohhara ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Mitsukuni Suenaga ◽  
Nobuyuki Mizunuma ◽  
...  

440 Background: Panitumumab has a high affinity for epidermal growth factor receptor. Its utility as a salvage therapy is unknown in cetuximab-resistant colorectal cancer. We assessed the prognostic and predictive role of circulating tumor cells (CTC) in KRAS wild-type metastatic colorectal cancer (mCRC) patients treated with panitumumab after progression of cetuximab. Methods: Panitumumab (6 mg/kg, every 2 weeks) was administered as a salvage therapy to cetuximab-resistant mCRC. CTCs of whole blood at baseline were isolated and enumerated using immunomagnetics. Results: Nineteen patients were enrolled in this prospective study between July 2010 and March 2011. Five patients had stable disease (SD) with a response rate of 0%. Four patients reached long SD, which was defined as continuous SD of more than 120 days. All of the four patients had <2 CTC. <2 CTC showed an independent predictive role for progression-free survival (PFS) at multivariate analysis (HR; 7.275, p=0.013). Patients with >2 CTC had shorter median PFS than those with <2 CTC (1.8 and 3.6 months, p=0.008). There was no statistical significance in median OS between patients with <2 CTC and those with >2 CTC (3.2 and 6.7 months, p=0.164). Conclusions: Panitumumab may be effective for patients with <2 CTC, KRAS-wild-type mCRC after progression of cetuximab.


2019 ◽  
Vol 156 (6) ◽  
pp. S-367-S-368
Author(s):  
Eun Young Park ◽  
Dong Hoon Baek ◽  
Gwang Ha Kim ◽  
Geun Am Song ◽  
Do Youn Park ◽  
...  

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.


Oncotarget ◽  
2016 ◽  
Vol 7 (37) ◽  
pp. 59058-59069 ◽  
Author(s):  
Wendy Onstenk ◽  
Anieta M. Sieuwerts ◽  
Bianca Mostert ◽  
Zarina Lalmahomed ◽  
Joan B. Bolt-de Vries ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10534-10534
Author(s):  
Jorge Barbazan ◽  
Lorena Alonso-Alconada ◽  
Laura Muinelo-Romay ◽  
Maria Vieito ◽  
Alicia Abalo ◽  
...  

10534 Background: Metastatic colorectal cancer (mCRC) relies on the detachment of aggressive malignant cells from the primary tumor into the bloodstream, being this Circulating Tumor Cells (CTC) the principal source of the further metastasis. Clinically, the presence of CTC is associated with poor prognosis and there exists a clear necessity for more specific and efficient chemotherapies in the treatment of mCRC. Our aim was to overcome this adverse scenario through the massive molecular profiling of the CTC population isolated from mCRC patients. Methods: CTC’s were magnetically isolated by using anti-EpCAM coupled magnetic beads from 6 mCRC patients and 3 healthy controls. The presence of CTCs was evaluated by citokeratins 8, 18 and 19 staining. RNA from CTCs was amplified by a whole transcriptome amplification system (WTA) and resulting material was hybridized onto gene expression arrays. Bioinformatics were used to array analysis. Selected genes were validated by RT-qPCR. Results: 410 transcripts were found to specifically characterise the CTC population after array signals comparison between mCRC patients and controls. Gene-gene interaction analysis generated networks related with cell migration, adhesion or apoptosis resistance. Gene ontology revealed similar functions. Signalling pathways such as RhoA, PKA, ILK, integrins or actin cytoskeleton signalling were found as relevant in CTCs. Eleven genes (TGFB1, APP, TIMP1, CD9, CLU, ITGB5, LIMS1, RSU1, VCL, BMP6 and TLN1) were validated by real-time PCR in 20 mCRC patient and 10 control samples. All genes showed a significantly higher expression in patients (p<0.0001). Except from TLN1 and CD9, all genes had a prognostic value in terms of progression free survival (p<0.05). Conclusions: We described the molecular profiling of CTCs in stage IV CRC patients, characterized by a migratory and invasive phenotype. Specific and sensitive diagnostic/prognostic markers were obtained. Our strategy represents an innovative and promising approach in the clinical management of mCRC patients.


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