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Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in Metastatic Colorectal Cancer
Authors:Giovanni Germano,Gianluca Mauri,Giulia Siravegna,Caroline Dive,Jackie Pierce,Federica Di Nicolantonio,Maurizio D&#x  Incalci,Alberto Bardelli,Salvatore Siena,Andrea Sartore-Bianchi
Affiliation:1. Candiolo Cancer Institute-FPO, IRCCS, Candiolo (TO), Italy;2. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy;3. Department of Oncology, University of Torino, Candiolo (TO), Italy;4. Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK;5. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy;6. Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy
Abstract:

Background

Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited.

Methods

We collected blood samples from 20 consecutive patients with mCRC with at least 1 of the following inclusion criteria: high tumor burden (> 1 metastasis), intact colonic primary tumor, disease progression at the time of sampling, ≤ 2 cycles of cytotoxic chemotherapy of current treatment course, and time between last chemotherapy cycle ≥ 4 weeks.

Results

Nineteen of 20 samples displayed the appropriate quality for CTC analysis. CTCs could be isolated in 7 (36.8%) of 19 evaluable patients. The median number of CTCs was 0 (range, 0-73). In 2 patients, we isolated > 1 CTC, and in five, we found 1 CTC. We retrieved ctDNA in all samples, with a median amount of 732,573 GE/mL (range, 174,774-174,078,615 GE/mL). Concordance between ctDNA and tissue for RAS, BRAF, and ERBB2 alterations was found in 11 (84.6%) of 13 cases.

Conclusions

In this cohort, we show that ctDNA was detectable in all cases, whereas CTCs were detectable in one-third of the cases. ctDNA analysis was achieved with a smaller amount of blood sampling and allowed molecular characterization. Our data indicate that ctDNA is a readily available candidate for clinical application in mCRC.
Keywords:Circulating tumor cells  Colorectal cancer  Liquid biopsy  RAS  Tumor heterogeneity
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