Giovanni Germano1, Gianluca Mauri2, Giulia Siravegna3, Caroline Dive4, Jackie Pierce4, Federica Di Nicolantonio3, Maurizio D'Incalci5, Alberto Bardelli3, Salvatore Siena6, Andrea Sartore-Bianchi7. 1. Candiolo Cancer Institute-FPO, IRCCS, Candiolo (TO), Italy. 2. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. 3. Candiolo Cancer Institute-FPO, IRCCS, Candiolo (TO), Italy; 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. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy. 7. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. Electronic address: andrea.sartorebianchi@ospedaleniguarda.it.
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.
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.
Authors: Jia Ge; Michael Y Liu; Lei Li; Qing Deng; Feng Liu; Ying Luo; Lihong Wang; Guangyin Yao; Dandan Zhu; Huimin Lu; Mei Liang; Song Deng; Rong Zhou; Tao Luo Journal: Int J Clin Exp Pathol Date: 2020-02-01
Authors: Richard A Jacobson; Emily Munding; Dana M Hayden; Mia Levy; Timothy M Kuzel; Sam G Pappas; Ashiq Masood Journal: Cancers (Basel) Date: 2019-08-13 Impact factor: 6.639
Authors: Manish Chand; Deborah S Keller; Reza Mirnezami; Marc Bullock; Aneel Bhangu; Brendan Moran; Paris P Tekkis; Gina Brown; Alexander Mirnezami; Mariana Berho Journal: World J Gastrointest Oncol Date: 2018-07-15
Authors: Pooja Ghatalia; Chad H Smith; Arthur Winer; Jiangtao Gou; Lesli A Kiedrowski; Michael Slifker; Patricia D Saltzberg; Nicole Bubes; Fern M Anari; Vineela Kasireddy; Asya Varshavsky; Yang Liu; Eric A Ross; Wafik S El-Deiry Journal: Front Oncol Date: 2019-01-17 Impact factor: 6.244