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INTRODUCTION: Analysis of circulating tumor DNA (ctDNA), also known as liquid biopsy, has been postulated to be a useful test in the prognostication, molecular profiling, and monitoring of cancer patients. In this series we aimed to analyze the concordance between the mutation status of formalin-fixed paraffin-embedded (FFPE) tumor samples and matched ctDNA, considering tumor molecular profiling as the gold standard technique. METHODS: This retrospective study included cancer patients with complete diagnostics and gene mutations detected in a previous FFPE tumor tissue Next-Generation Sequencing (NGS) study with a matched frozen plasma sample available for an NGS ctDNA assay. RESULTS AND DISCUSSION: Sixty patients were included, 24 with colorectal carcinoma (CRC) and 36 with non-small cell lung cancer (NSCLC). In 27.1% of ctDNA studies a new mutation not previously detected in the matched tumor was found. 11.9% of these ctDNA results had the potential to impact clinical management. Globally, the concordance rate between FFPE tumor samples and ctDNA was 44.4%. When tumors were stratified by stage, the concordance was 76.5%, 70%, 36.4%, and 0% in tumor stages IV, III, II, and I, respectively. ctDNA molecular profiles showed a good concordance rate in advanced stage tumors and identified undetected mutations in tumor tissues. In early tumor stages the concordance was low, casting doubt on the usefulness of ctDNA in these patients.

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RESUMEN

Introduction: Analysis of circulating tumor DNA (ctDNA), also known as liquid biopsy, has been postulated to be a useful test in the prognostication, molecular profiling, and monitoring of cancer patients. In this series we aimed to analyze the concordance between the mutation status of formalin-fixed paraffin-embedded (FFPE) tumor samples and matched ctDNA, considering tumor molecular profiling as the gold standard technique. Methods: This retrospective study included cancer patients with complete diagnostics and gene mutations detected in a previous FFPE tumor tissue Next-Generation Sequencing (NGS) study with a matched frozen plasma sample available for an NGS ctDNA assay. Results and discussion: Sixty patients were included, 24 with colorectal carcinoma (CRC) and 36 with non-small cell lung cancer (NSCLC). In 27.1% of ctDNA studies a new mutation not previously detected in the matched tumor was found. 11.9% of these ctDNA results had the potential to impact clinical management. Globally, the concordance rate between FFPE tumor samples and ctDNA was 44.4%. When tumors were stratified by stage, the concordance was 76.5%, 70%, 36.4%, and 0% in tumor stages IV, III, II, and I, respectively. ctDNA molecular profiles showed a good concordance rate in advanced stage tumors and identified undetected mutations in tumor tissues. In early tumor stages the concordance was low, casting doubt on the usefulness of ctDNA in these patients.(AU)

Introducción: Se ha postulado que el análisis de ADN tumoral circulante (ctDNA), conocido también como biopsia líquida, es una prueba útil a la hora de pronosticar, elaborar el perfilado molecular, y supervisar a los pacientes de cáncer. En esta serie nuestro objetivo fue analizar la concordancia entre el estatus mutacional de las muestras tumorales (formalin-fixed paraffin-embedded) y el ctDNA equiparado, considerando el perfilado molecular del tumor la técnica de referencia. Métodos: Este estudio retrospectivo incluyó pacientes de cáncer con diagnóstico completo y mutaciones genéticas detectadas en un estudio anterior de NGS de tejido tumoral formalin-fixed paraffin-embedded con una muestra equiparada de plasma congelado disponible para un ensayo ctDNA mediante NGS. Resultados y discusión: Incluimos sesenta pacientes: 24 con cáncer colorrectal y 36 con cáncer de pulmón de células no pequeñas (NSCLC). En el 27,1% de los estudios de ctDNA se encontró una nueva mutación no detectada previamente en el tumor equiparado. El 11,9% de dichos resultados de ctDNA tenía potencial de repercutir en el manejo clínico. A nivel global, la tasa de concordancia entre las muestras tumorales formalin-fixed paraffin-embedded y ctDNA fue del 44,4%. Al estratificar los tumores por estadio, la concordancia fue del 76,5%, 70%, 36,4%, y 0% para los estadios tumorales IV, III, II, y I, respectivamente. Los perfiles moleculares de ctDNA reflejaron una buena tasa de concordancia en tumores de estadio avanzado, e identificaron mutaciones no detectadas en los tejidos tumorales. En los estadios tumorales tempranos la concordancia fue baja, planteando dudas sobre la utilidad de ctDNA en dichos pacientes.(AU)

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