Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients
Daniele Lavacchi,
Stefania Gelmini,
Adele Calabri,
Gemma Rossi,
Lisa Simi,
Enrico Caliman,
Irene Mancini,
Francesca Salvianti,
Giulia Petroni,
Alessia Guidolin,
Federico Scolari,
Luca Messerini,
Serena Pillozzi,
Pamela Pinzani,
Lorenzo Antonuzzo
Affiliations
Daniele Lavacchi
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
Stefania Gelmini
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
Adele Calabri
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
Gemma Rossi
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
Lisa Simi
Clinical and Molecular Biochemistry Careggi University Hospital, Florence, Italy
Enrico Caliman
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
Irene Mancini
Clinical and Molecular Biochemistry Careggi University Hospital, Florence, Italy
Francesca Salvianti
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
Giulia Petroni
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Alessia Guidolin
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
Federico Scolari
Department of Health Science, University of Florence, Florence, Italy
Luca Messerini
Pathology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Serena Pillozzi
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Pamela Pinzani
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy; Clinical and Molecular Biochemistry Careggi University Hospital, Florence, Italy
Lorenzo Antonuzzo
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Corresponding author. Clinical Oncology Unit and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
The detection of RAS mutations and co-mutations in liquid biopsy offers a novel paradigm for the dynamic management of metastatic colorectal cancer (mCRC) patients.Expanding the results of the prospective OMITERC (OMIcs application from solid to liquid biopsy for a personalized ThERapy of Cancer) project, we collected blood samples at specific time points from patients who received a first-line chemotherapy (CT) for KRAS-mutated mCRC. CTC quantification was performed by CellSearch® system. Libraries from cfDNA were prepared using the Oncomine™ Colon cfDNA Assay to detect tumour-derived DNA in cfDNA. The analysis involved >240 hotspots in 14 genes.Twenty patients with KRAS-mutated mCRC treated at the Medical Oncology Unit of Careggi University Hospital were prospectively enrolled. Nine patients had available data for longitudinal monitoring of cfDNA. After 6 weeks of first-line CT an increase of KRAS-mutated clone was reported in the only patient who did not obtain disease control, while all patients with decrease of KRAS clones obtained disease control. Overall, in patients with a short (<9 months) progression-free survival (PFS) we registered, at 6 weeks, an increase in cfDNA levels and in KRAS mutations or other co-mutations, i.e. PIK3CA, FBXW7, GNAS, and TP53. In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones.In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC.
