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COMPLEMENTING NGS TISSUE BIOPSY WITH PLASMA DERIVED cFNA ANALYSIS AS A LIQUID BIOPSY FOR REAL-TIME THERAPY MODULATION IN COLORECTAL CANCER PATIENTS

MARIUS ZAMFIR ^1,2#, ALEXANDRA PUȘCAȘU ^3,4, ARIANA HUDIȚĂ ³*, BIANCA GĂLĂȚEANU ³, LAURA BUBURUZAN ⁵, ANCA MARIA IROFEI ⁵, CONSTANTIN BUSUIOC ⁶, MARA MARDARE ^1,2,7, ALEXANDRU FILIPPI ⁸, GEORGE-TRAIAN-ALEXANDRU BURCEA-DRAGMIROIU ⁹, MIHAI TĂNASE ¹⁰, FLORIN GRAMA ¹¹, NICULAE IORDACHE ⁷#, OCTAV GINGHINĂ ^2,7, BOGDAN-COSMIN TĂNASE 12

1Doctoral School of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
² Department of Surgery 3, “Prof. Dr. A. Trestioreanu” Institute of Oncology Bucharest, 022328, Bucharest, Romania
³ Department of Biochemistry and Molecular Biology, University of Bucharest, 050095, Bucharest, Romania
⁴ “Sfântul Ioan cel Nou” County Emergency Clinical Hospital, 720224, Suceava, Romania
⁵ Department of Molecular Biology, Oncoteam Diagnostic SA, 010719, Bucharest, Romania
⁶ Department of Pathology, “Prof Dr Matei Balș” National Institute of Infectious Diseases, 021105, Bucharest, Romania
⁷ Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
⁸ Departament of Biochemistry and Biophysics, “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
⁹ Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
¹⁰ Department of Surgery 1, “Carol Davila” Central Military Emergency University Hospital, 010825, Bucharest, Romania
¹¹ Department of General Surgery, Colțea Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 030171, Bucharest, Romania
¹² Department of Thoracic Surgery, “Prof. Dr. A. Trestioreanu” Institute of Oncology Bucharest, 022328, Bucharest, Romania

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Currently, treatment strategies for colorectal cancer (CRC) are primarily guided by cancer staging, patient performance status, molecular profiling and mismatch repair status. Therapeutic modalities include surgery, systemic chemotherapy, radiation therapy, targeted therapy and immunotherapy. The emergence of liquid biopsy, which involves analysing tumour-derived analytes in body fluids, promises to reshape patient diagnosis and management due to its minimally invasive nature, rapid results and ability to account for tumour heterogeneity. In this context, the aim of the current study is to investigate liquid biopsy as an instrument for prognosis and therapy modulation, primarily through a comparative analysis of the mutational landscape of CRC in tumour tissue and liquid biopsy samples. Our results demonstrated that a considerable number of plasma mutations can be detected using liquid biopsies, with a detection rate of 38.7% (12 out of 31). The ability of liquid biopsies to identify mutations is significantly correlated with the degree of invasion of the primary tumour into the gastrointestinal wall (T), confirming that the more locally advanced the disease, the higher the plasma tumour burden and the more informative the genetic analysis.