Circulating tumor DNA tracking in patients with pancreatic cancer using next-generation sequencing / Evaluación de DNA circulante tumoral en paciente con Cáncer de páncreas empleando secuenciación de nueva generación

Background: Pancreatic cancer remains one of the most devastating malignancies due to the absence of techniques for early diagnosis and the lack of target therapeutic options for advanced disease. Next Generation Sequencing (NGS) generates high throughput and valuable genetic information when evaluating circulating tumor DNA (ctDNA); however clinical utility of liquid biopsy in pancreatic cancer has not been demonstrated yet. The aim of this study was to evaluate whether results from a Next Generation Sequencing panel on plasma samples from pancreatic cancer patients could have a clinical significance. Methods: From December 2016 to January 2020, plasma samples from 27 patients with pancreatic ductal adenocarcinoma at two different tertiary Spanish Hospitals underwent ctDNA testing using a commercial NGS panel of 65 genes. Clinical data were available for these patients. VarsSome Clinical software was used to analyse NGS data and establish pathogenicity. Results: Evaluable NGS results were obtained in 18 out of the 27 plasma samples. Somatic pathogenic mutations were found mainly in KRAS, BRCA2, FLT3 and HNF1A, genes. Pathogenic mutations were detected in 50% of plasma samples from patient diagnosed at stages III-IV samples. FLT3 mutations were observed in 22.22% of samples which constitute a novel result in the field. Conclusions: Liquid biopsy using NGS is a valuable tool but still not sensitive or specific enough to provide clinical utility in pancreatic cancer patients.(AU)

Introducción: El cáncer de páncreas es uno de los cánceres más devastadores debido a la falta de métodos que permitan un diagnóstico temprano y la ausencia de opciones terapéuticas en enfermedad avanzada. La técnica de secuenciación de nueva generación o Next Generation Sequencing (NGS) proporciona importantes resultados de alto rendimiento de información genética en muestras de DNA circulante tumoral (ctDNA); sin embargo, la utilidad clínica de la biopsia líquida en cáncer de páncreas no ha sido demostrado todavía. El objetivo de este estudio fue evaluar si los resultados de un panel de secuenciación de nueva generación en muestras de plasma de pacientes con cáncer de páncreas podría tener un significado clínico. Métodos: Empleando un panel comercial de NGS con 65 genes se evaluaron 27 muestras de plasma de pacientes con cáncer de páncreas recogidas entre diciembre del 2016 y enero del 2020 en 2 hospitales españoles. En el estudio se disponía de datos clínicos correspondientes a los pacientes. Se empleó el software VarSome Clinical para analizar resultados y establecer patogenicidad de las variantes. Resultados: Se obtuvieron resultados evaluables en 18 de las 27 muestras de plasma. Se encontraron mutaciones patogénicas en los genes KRAS, BRCA2, FLT3 y HNF1A. El 50% de los pacientes diagnosticados en estadios ii-iv presentaron alteraciones patogénicas en plasma. Se observaron mutaciones en FLT3 en el 22,22% de las muestras, lo cual es un resultado novedoso. Conclusiones: La NGS en biopsia líquida es una herramienta valiosa pero todavía no sensible ni específica para proporcionar utilidad clínica en pacientes con cáncer de páncreas.(AU)

Circulating tumor DNA tracking in patients with pancreatic cancer using next-generation sequencing.

BACKGROUND: Pancreatic cancer remains one of the most devastating malignancies due to the absence of techniques for early diagnosis and the lack of target therapeutic options for advanced disease. Next Generation Sequencing (NGS) generates high throughput and valuable genetic information when evaluating circulating tumor DNA (ctDNA); however clinical utility of liquid biopsy in pancreatic cancer has not been demonstrated yet. The aim of this study was to evaluate whether results from a Next Generation Sequencing panel on plasma samples from pancreatic cancer patients could have a clinical significance. METHODS: From December 2016 to January 2020, plasma samples from 27 patients with pancreatic ductal adenocarcinoma at two different tertiary Spanish Hospitals underwent ctDNA testing using a commercial NGS panel of 65 genes. Clinical data were available for these patients. VarsSome Clinical software was used to analyse NGS data and establish pathogenicity. RESULTS: Evaluable NGS results were obtained in 18 out of the 27 plasma samples. Somatic pathogenic mutations were found mainly in KRAS, BRCA2, FLT3 and HNF1A, genes. Pathogenic mutations were detected in 50% of plasma samples from patient diagnosed at stages III-IV samples. FLT3 mutations were observed in 22.22% of samples which constitute a novel result in the field. CONCLUSIONS: Liquid biopsy using NGS is a valuable tool but still not sensitive or specific enough to provide clinical utility in pancreatic cancer patients.

Retrievability of uncoated versus paclitaxel-coated Günther-Tulip IVC filters in an animal model.

PURPOSE: To compare in a pilot study, the retrievability and inferior vena cava (IVC) wall reaction elicited by uncoated and paclitaxel-coated Günther-Tulip filters in the animal model. MATERIALS AND METHODS: Three groups with five pigs each underwent infrarenal IVC implantation of Günther-Tulip filters. Paclitaxel-coated filters were used in Groups A and B and uncoated filters were used in Group C. Filters were removed at 14, 19, 22, 26, and 30 days after implantation. A laparotomy was performed to remove filters from animals in group A and filters from animals in groups B and C that could not be retrieved via the right transjugular approach. Filter-induced venous wall changes were evaluated by examination of IVC venography, feasibility of filter removal at different implantation times, and laparotomy and microscopic findings. Feasibility of filter retrieval and venous wall changes were correlated. RESULTS: IVC cavography showed no abnormality. Filters in animals in group B were uneventfully removed by a right jugular approach. Uncoated filter removal was not feasible in three of five animals in group C (19, 22, and 26 days). Microscopically, animals in group A had absent filter-induced IVC wall changes at 14, 19, 22, and 26 days and minimal changes at 30 days post implantation; animals in group B had absent filter-induced IVC wall changes at 14, 19, and 22 days and minimal changes at 26 and 30 days; animals in group C had moderate filter-induced IVC wall changes at 14 days and severe changes at 19, 22, 26, and 30 days. CONCLUSIONS: This pilot study suggests that endothelial reaction to the presence of IVC filters in the porcine model is diminished by addition of paclitaxel coating to these filters. Further studies are necessary to substantiate these results.