Analytical performance of the FDA-cleared Parsortix® PC1 system.

Introduction: The Parsortix® PC1 system, Food and Drug Administration (FDA) cleared for use in metastatic breast cancer (MBC) patients, is an epitope-independent microfluidic device for the capture and harvest of circulating tumor cells from whole blood based on cell size and deformability. This report details the analytical characterization of linearity, detection limit, precision, and reproducibility for this device. Methods: System performance was determined using K2-EDTA blood samples collected from self-declared healthy female volunteers (HVs) and MBC patients spiked with prelabeled cultured breast cancer cell lines (SKBR3, MCF7, or Hs578T). Samples were processed on Parsortix® PC1 systems and captured cells were harvested and enumerated. Results: The system captured and harvested live SKBR3, MCF7, and Hs578T cells and fixed SKBR3 cells linearly between 2 and ~100 cells, with average harvest rates of 69%, 73%, 79%, and 90%, respectively. To harvest ≥1 cell ≥95% of the time, the system required 3, 5 or 4 live SKBR3, MCF7 or Hs578T cells, respectively. Average harvest rates from precision studies using 5, 10, and ~50 live cells spiked into blood for each cell line ranged from 63.5% to 76.2%, with repeatability and reproducibility percent coefficient of variation (%CV) estimates ranging from 12.3% to 32.4% and 13.3% to 34.1%, respectively. Average harvest rates using ~20 fixed SKBR3 cells spiked into HV and MBC patient blood samples were 75.0% ± 16.1% (%CV = 22.3%) and 68.4% ± 14.3% (%CV = 21.1%), respectively. Conclusions: These evaluations demonstrate the Parsortix® PC1 system linearly and reproducibly harvests tumor cells from blood over a range of 1 to ~100 cells.

Phenotypic Plasticity in Circulating Tumor Cells Is Associated with Poor Response to Therapy in Metastatic Breast Cancer Patients.

Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC counts decreased with therapy, and progressors had higher CTC counts than non-progressors. CTC count was prognostic primarily at the start of therapy in univariate and multivariate analyses but had less prognostic utility at 6 months to 1 year later. In contrast, gene expression, including both epithelial and mesenchymal markers, identified high-risk patients after 6-9 months of treatment, and progressors had a shift towards mesenchymal CTC gene expression on therapy. Cross-sectional analysis showed higher CTC-related gene expression in progressors 6-15 months after baseline. Furthermore, patients with higher CTC counts and CTC gene expression experienced more progression events. Longitudinal time-dependent multivariate analysis indicated that CTC count, triple-negative status, and CTC expression of FGFR1 significantly correlated with inferior progression-free survival while CTC count and triple-negative status correlated with inferior overall survival. This highlights the utility of protein-agnostic CTC enrichment and multimodality analysis to capture the heterogeneity of CTCs.

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer.

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC. Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase chain reaction (RT-PCR) using a customized pre-selected panel of 20 genes. Results: At least 1 CTC was detected by enumeration in 53.8% of samples. Most patients had fewer than 5 CTCs (91%) and the highest observed count was 35 CTCs. Enumeration of single CTCs was not prognostic, although detection of CTC clusters at any time point was associated with increased risk of progression [hazard ratio (HR) 3.00, 95% confidence interval (CI): 1.1-8.2, P=0.0318]. In contrast, 124 (97.6%) patients with samples interrogated for gene expression had at least 1 gene detectable in at least 1 sample, and 101 (79.5%) had at least one elevated epithelial gene in at least one timepoint. High expression of BCL2, CD274 [programmed death-ligand 1 (PD-L1)], CDH1, EPCAM, FGFR1, FN1, KRT18, MET and MUC1 were associated with poor prognosis. Patients with CTCs positive for at least 3 epithelial genes at baseline all progressed within 10 months (HR 8.2, P<0.001, 95% CI: 3.2-21.1). BCL2, CD274 (PD-L1), EPCAM and MUC1 remained significant independent prognostic factors in multivariate, time-dependent analyses of progression and death. Conclusions: The selective profile of CTC genes and identification of CTC clusters better correlated with prognosis than enumeration of enriched CTC in NSCLC patients in this study.

Resultados del tratamiento quirúrgico en pacientes con cáncer colorrectal avanzado / Outcomes of Surgical Treatment in Patients with Advanced Colorectal Cancer

RESUMEN Introducción: El cáncer avanzado es aquel que crece fuera del órgano en el cual se originó. La resección quirúrgica es el método más eficaz para lograr la curación de cáncer colorrectal en 50 por ciento de los casos. Objetivo: Evaluar los resultados del tratamiento multidisciplinar, realizado a pacientes con diagnóstico de cáncer colorrectal avanzado. Método: Se realizó un estudio observacional, descriptivo, ambispectivo y de corte transversal en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras" entre enero de 2013 y diciembre de 2018. La muestra fue de 219 casos. Resultados: El 34,2 por ciento de los pacientes tenían entre 70 y 79 años. Hubo predominio de localización en colon ascendente (37,4 por ciento), en 57,1 por ciento fue moderadamente diferenciado y en 34,2 por ciento en estadio IIIA. El 7,8 por ciento de los pacientes tuvo recaída con metástasis, de ellos, 70,5 por ciento en hígado. En 72,6 por ciento la vía de acceso fue laparoscópica. En 50,7 por ciento se realizó hemicolectomía derecha. Las complicaciones se observaron en 25 pacientes (35,2 por ciento). El 91,3 por ciento de los casos recibió terapia adyuvante. En 27,4 por ciento hubo recurrencia. En el análisis del tiempo libre de enfermedad y de la supervivencia se obtuvieron buenos resultados. Conclusiones: El tratamiento combinado, secuencial y multidisciplinario en enfermedad maligna colorrectal avanzada ha demostrado beneficios clínicos y mayor supervivencia. Con una morbilidad y mortalidad relacionada con el proceder quirúrgico aceptable independientemente la vía de acceso empleada(AU)

ABSTRACT Introduction: advanced cancer is cancer that has grown outside the organ in which it originated. Surgical resection is the most effective method to achieve colorectal cancer cure in 50 % of cases. Objectives: the objective was to evaluate the results of the multidisciplinary treatment, carried out on patients diagnosed with advanced colorectal cancer. Method: it is an observational, descriptive, ambispective and cross-sectional study at the "Hermanos Ameijeiras" Surgical Clinical Hospital between January 2013 and December 2018. The sample was 219 cases. Results: 34.2 percent of the patients were between 70 and 79 years old. 56.2 percent were women. There was a predominance of localization in the ascending colon (37.4 percent), in 57.1 percent it was moderately differentiated and in 34.2 percent in stage IIIA. 7.8 percent of the patients had a metastatic relapse, 70.5 percent of them in the liver. In 72.6 percent, the access route was laparoscopic. Right hemicolectomy was performed in 50.7 percent. Complications were observed in 25 patients (35.2 percent). 91.3 percent of the cases received adjuvant therapy. In 27.4 percent there was recurrence. Good results were obtained in the analysis of disease-free time and survival. Conclusion: we conclude that combined, sequential, and multidisciplinary treatment in advanced colorectal malignancy has demonstrated clinical benefits and increased survival. With an acceptable morbidity and mortality related to the surgical procedure regardless of the access route used. Multivisceral and / or en bloc resections and maximum resection manage to increase the free interval of disease progression and alleviate symptoms(AU)

Onicólisis en el curso de la artropatía psoriásica. Presentación de un caso / Onycholysis in the course of psoriatic arthropathy. Presentation of a case

Las lesiones dermatológicas que se presentan en el curso de la antipatía psoriásica son diversas, entre ellas las manifestaciones ungüeales son características y con frecuencia facilitan el razonamiento médico y ayudan al diagnóstico nosológico de esta entidad; se presenta un paciente que a punto de partida de las lesiones onicolíticas de las uñas de los pie, oriento al estudio de otros elementos de laboratorio concluyendo como una de una artropatía psoriásica con seis puntos de la clasificación de Caspar para el estudio de esta entidad.

The dermatological lesions that occur in the course of psoriatic arthropathy are diverse, among which ungüeal manifestations are characteristic and often facilitate medical reasoning and help nosological diagnosis; a patient is presented who, starting point of the onicolitic lesions of the nails of the foot, is directed to the study of other laboratory elements, concluding as one of a psoriatic arthropathy with six points of the Caspar classification for the study of this entity.