Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study

Immune checkpoint inhibitors; Immunotherapy; Solid tumorsInhibidores de puntos de control inmunitarios; Inmunoterapia; Tumores sólidosInhibidors del punt de control immunitari; Immunoteràpia; Tumors sòlidsImmune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored

Determinación de la frecuencia del funcionamiento del acceso vascular mediante la curva de contractilidad en pacientes hemodializados en el Hospital José Carrasco Arteaga, Cuenca-Ecuador, 2012

Antecedentes: El acceso vascular es una condición de uso frecuente en pacientes con insuficiencia renal, cuyo uso está establecido según evidencias científicamente comprobadas. Sin embargo, desconocemos en nuestro medio la frecuencia del funcionamiento de los distintos tipos de accesos. Objetivo: Determinar la frecuencia del funcionamiento del acceso vascular mediante la medición de flujos extracorpóreos en pacientes sometidos a hemodiálisis en el hospital José Carrasco Arteaga de la ciudad de Cuenca en el año 2013. Diseño Metodológico: El presente estudio es de tipo descriptivo, con una muestra de 74 pacientes. Se tomó en cuenta variables como el tipo de acceso vascular, localización, complicaciones y medición de flujos extracorpóreos en las líneas arterial y venosa. Los datos se obtuvieron por medio del registro observacional para su análisis ulterior con los programas SPSS y Excel. Resultados: La media de edad se ubicó en 56,80 años, con distribución 50-50 para ambos sexos; en el 50% de la población el acceso vascular fue la fístula; La principal localización del acceso vascular fue la extremidad superior distal con el 31,1% de los casos. Intradiálisis los flujos extracorpóreos para el percentil 50 fueron, DALP -60mmHg 126 ml/min; DALP -100mmHg 182 ml/min; DALP -160mmHg 243 ml/min; DALP -200mmHg 283 ml/min y DALP -260mmHg 328 ml/min. La fístula arterio-venosa presentó mejores flujos extracorpóreos. La frecuencia de complicaciones del funcionamiento del acceso vascular fue del 6,8. Conclusiones: La curva de contractilidad es un buen método para determinar la funcionalidad del acceso vascular. PALABRAS CLAVE: ACCESO VASCULAR – FÍSTULA – CATÉTER – CURVA DE CONTRACTILIDADAntecedent: Vascular access is a common practice used among patients suffering from renal insufficiency. Its use has been established according to clear and scientifically proven evidence. However, unknown in our operating frequency of the different types of vascular access. Objective: To utilize the contractility curve in order to determine the frequency the performance of the vascular access. It’s functionality was assessed by measuring extracorporeal flow in patients undergoing hemodialysis. The analysis was performed at José Carrasco Arteaga Hospital in Cuenca city in 2013. Methodology Design: The is study characterized as descriptive. It was performed during the month from November 2012 to May 2013. The sample population consisted of 74 patients undergoing hemodialysis treatment at the José Carrasco Arteaga Hospital. Variables such as vascular access types, its locations, complications and measurement of extracorporeal flows in the arterial and venous lines were considered in the study. The data utilized was extracted from the observational registry and entered in the system for further analysis with SPSS and Excel programs. Results: The mean age was 56.80 years. The distribution was 50-50 ratio for both sexes. In 50% of the population the vascular access was a fistula. In this sample population, a total of 31,1 % of cases the main location of vascular access in the upper distal extremity. The Intradialytic extracorporeal flows to the 50th percentile were, DALP-60mmHg 126 ml/min; DALP -100mmHg 182 ml/min, DALP- 160mmHg 243ml/min; DALP-200mmHg 283 ml/min and DALP -260mmHg 328 ml/min. The arterio-venous catheters in comparison to the extracorporeal flows presented better extracorporeal flows. The operating frequency of complications of vascular access was 6.8% of total patients. Conclusion: The contractile curve in patients undergoing hemodialysis is an accurate method to determine the performance of vascular access. KEY WORDS: VASCULAR ACCESS, FISTULA, CATHETERS, CONTRACTILE CURVEMédicoCuenc