Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Plasma ctDNA Analysis at T0
2.2. Plasma ctDNA Analysis at T1
2.3. Plasma ctDNA Analysis at First-Line PD (T2)
2.4. Plasma ctDNA Analysis at Second-Line PD (T3)
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Said, R.; Guibert, N.; Oxnard, G.R.; Tsimberidou, A.M. Circulating tumor DNA analysis in the era of precision oncology. Oncotarget 2020, 11, 188–211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheng, M.L.; Pectasides, E.; Hanna, G.J.; Parsons, H.A.; Choudhury, A.D.; Oxnard, G.R. Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions. CA A Cancer J. Clin. 2020. [Google Scholar] [CrossRef]
- Internò, V.; Tucci, M.; Pezzicoli, G.; Silvestris, F.; Porta, C.; Mannavola, F. Liquid biopsy as a tool exploring in real-time both genomic perturbation and resistance to EGFR antagonists in colorectal cancer. Front. Oncol. 2020, 10, 1–12. [Google Scholar] [CrossRef]
- Siravegna, G.; Mussolin, B.; Venesio, T.; Marsoni, S.; Seoane, J.; Dive, C.; Papadopoulos, N.; Kopetz, S.; Corcoran, R.; Siu, L.; et al. How liquid biopsies can change clinical practice in oncology. Ann. Oncol. 2019, 30, 1580–1590. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raimondi, C.; Nicolazzo, C.; Belardinilli, F.; Loreni, F.; Gradilone, A.; Mahdavian, Y.; Gelibter, A.; Giannini, G.; Cortesi, E.; Gazzaniga, P. Transient disappearance of RAS mutant clones in plasma: A counterintuitive clinical use of EGFR inhibitors in RAS mutant metastatic colorectal cancer. Cancers 2019, 11, 42. [Google Scholar] [CrossRef] [Green Version]
- Gazzaniga, P.; Raimondi, C.; Nicolazzo, C.; Gradilone, A.; Cortesi, E. ctDNA might expand therapeutic options for second line treatment of KRAS mutant mCRC. Ann. Oncol. 2017, 28, v586. [Google Scholar] [CrossRef]
- Gazzaniga, P.; Raimondi, C.; Urbano, F.; Cortesi, E. Second line EGFR-inhibitors in RAS mutant metastatic colorectal cancer: The plasma RAS wild type “window of opportunity”. Ann. Oncol. 2018, 29, viii183–viii184. [Google Scholar] [CrossRef]
- Barault, L.; Amatu, A.; Siravegna, G.; Ponzetti, A.; Moran, S.; Cassingena, A.; Mussolin, B.; Falcomatà, C.; Binder, A.M.; Cristiano, C.; et al. Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer. Gut 2017, 67, 1995–2005. [Google Scholar] [CrossRef] [PubMed]
- Amatu, A.; Schirripa, M.; Tosi, F.; Lonardi, S.; Bencardino, K.; Bonazzina, E.; Palmeri, L.; Patanè, D.A.; Pizzutilo, E.G.; Mussolin, B.; et al. High circulating methylated DNA is a negative predictive and prognostic marker in metastatic colorectal cancer patients treated with regorafenib. Front. Oncol. 2019, 9, e622. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Cutsem, E.; Cervantes, A.; Adam, R.; Sobrero, A.; Van Krieken, J.H.; Aderka, D.; Aranda Aguilar, E.; Bardelli, A.; Benson, A.; Bodoky, G.; et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann. Oncol. 2016, 27, 1386–1422. [Google Scholar] [CrossRef] [PubMed]
- Gazzaniga, P.; Raimondi, C.; Urbano, F.; Cortesi, E. EGFR Inhibitor as second-line therapy in a patient with mutant RAS metastatic colorectal cancer: Circulating tumor DNA to personalize treatment. JCO Precis. Oncol. 2018, 2, 1–6. [Google Scholar] [CrossRef] [Green Version]
- Fernández Montes, A.; Martinez Lago, D.; De la Cámara Gómez, J.; Covela Rúa, M.; Cousillas Castiñeiras, A.; Gonzalez Villarroel, P.; Méndez Méndez, J. FOLFIRI plus panitumumab as second-line treatment in mutated RAS metastatic colorectal cancer patients who converted to wild type RAS after receiving first-line FOLFOX/CAPOX plus bevacizumab-based treatment: Phase II CONVERTIX trial. Ann. Oncol. 2019, 30, iv23–iv24. [Google Scholar] [CrossRef]
- Klein-Scory, S.; Wahner, I.; Maslova, M.; Al-Sewaidi, Y.; Pohl, M.; Mika, T.; Ladigan, S.; Schroers, R.; Baraniskin, A. Evolution of RAS mutational status in liquid biopsies during first-line chemotherapy for metastatic colorectal cancer. Front. Oncol. 2020, 10, e1115. [Google Scholar] [CrossRef]
- Bouchahda, M.; Saffroy, R.; Karaboué, A.; Hamelin, J.; Innominato, P.; Saliba, F.; Lévi, F.; Bosselut, N.; Lemoine, A. Undetectable RAS-mutant clones in plasma: Possible implication for anti-EGFR therapy and prognosis in patients with RAS-mutant metastatic colorectal cancer. JCO Precis Oncol 2020, 4, 1070–1079. [Google Scholar] [CrossRef] [PubMed]
- Vidal, J.; Muinelo, L.; Dalmases, A.; Jones, F.; Edelstein, D.; Iglesias, M.; Orrillo, M.; Abalo, A.; Rodríguez, C.; Brozos, E.; et al. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann. Oncol. 2017, 28, 1325–1332. [Google Scholar] [CrossRef] [PubMed]
- Dasari, A.; Morris, V.K.; Allegra, C.J.; Atreya, C.; Benson, A.B., 3rd; Boland, P.; Chung, K.; Copur, M.S.; Corcoran, R.B.; Deming, D.A.; et al. ctDNA applications and integration in colorectal cancer: An NCI Colon and Rectal-Anal Task Forces whitepaper. Nat. Rev. Clin. Oncol. 2020, 17, 757–770. [Google Scholar] [CrossRef] [PubMed]
- Diaz, L.A.; Bardelli, A. Liquid Biopsies: Genotyping Circulating Tumor DNA. J. Clin. Oncol. 2014, 32, 579–586. [Google Scholar] [CrossRef] [PubMed]
- Bach, S.; Sluiter, N.R.; Beagan, J.J.; Mekke, J.M.; Ket, J.C.F.; Van Grieken, N.C.T.; Steenbergen, R.D.; Ylstra, B.; Kazemier, G.; Tuynman, J.B. Circulating tumor DNA analysis: Clinical implications for colorectal cancer patients. A systematic review. JNCI Cancer Spectr. 2019, 3, pkz042. [Google Scholar] [CrossRef] [PubMed]
- Mathai, R.A.; Vidya, R.V.S.; Reddy, B.S.; Thomas, L.; Udupa, K.S.; Kolesar, J.; Rao, M. Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors: Implications in the precision oncology. J. Clin. Med. 2019, 8, 373. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cescon, D.W.; Bratman, S.V.; Chan, S.M.; Siu, L.L. Circulating tumor DNA and liquid biopsy in oncology. Nat. Rev. Cancer 2020, 1, 276–290. [Google Scholar] [CrossRef]
Patient | Age | Gender | Primary Location | Tissue RAS Status | 1st Line Therapy | Metastatic Site at 1st PD | 2nd Line Therapy | Metastatic Site at 2nd PD |
---|---|---|---|---|---|---|---|---|
1 | 68 | M | Right | KRAS G12D | Folfoxiri/Bev | Lung/Peritoneum | TAS-102 | N.A. † |
2 | 66 | M | Left | KRAS G12V | Folfiri/Bev | Liver/Nodes | Folfox/Bev | Liver/Lung |
3 | 76 | F | Rectum | KRAS G12V | Folfox/Bev | Liver/Nodes | Folfiri/Bev | Liver/Lung |
4 | 58 | F | Right | KRAS G12C | Folfoxiri/Bev | Lung | TAS-102 | Brain |
5 | 65 | F | Right | NRAS G12D | Folfiri/Bev | Liver | Folfox/Bev | N.A. † |
6 | 78 | M | Left | KRAS G13D | Folfiri/Bev | Liver */Lung | Folfox/Bev | N.A. † |
7 | 62 | F | Rectum | KRAS G12V | Folfox/Bev | Liver/Lung | Folfiri/Bev | Liver/Lung |
8 | 47 | M | Rectum | NRAS A146T | Folfoxiri/Bev | Lung | Folfiri/Aflibercept | Liver/Lung |
9 | 76 | M | Left | NRAS Q61R | Folfoxiri/Bev | Liver/Nodes | Folfiri/Aflibercept | Lung |
10 | 58 | M | Right | KRAS G12C | Folfox/Bev | Liver/Lung | Folfiri/Bev | Lung |
11 | 64 | M | Left | KRAS G12C | Folfiri/Bev | Liver/Lung | Folfiri/Aflibercept | Lung/Peritoneum |
12 | 60 | F | Right | KRAS G12D | Folfox/Bev | Brain/Lung | Folfiri/Bev | Brain/Lung |
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Nicolazzo, C.; Barault, L.; Caponnetto, S.; Macagno, M.; De Renzi, G.; Gradilone, A.; Belardinilli, F.; Cortesi, E.; Di Nicolantonio, F.; Gazzaniga, P. Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients. Cancers 2020, 12, 3633. https://doi.org/10.3390/cancers12123633
Nicolazzo C, Barault L, Caponnetto S, Macagno M, De Renzi G, Gradilone A, Belardinilli F, Cortesi E, Di Nicolantonio F, Gazzaniga P. Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients. Cancers. 2020; 12(12):3633. https://doi.org/10.3390/cancers12123633
Chicago/Turabian StyleNicolazzo, Chiara, Ludovic Barault, Salvatore Caponnetto, Marco Macagno, Gianluigi De Renzi, Angela Gradilone, Francesca Belardinilli, Enrico Cortesi, Federica Di Nicolantonio, and Paola Gazzaniga. 2020. "Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients" Cancers 12, no. 12: 3633. https://doi.org/10.3390/cancers12123633