Long-term Clinical Outcomes of a Spanish Cohort of Metastatic Renal Cell Carcinoma Patients with a Complete Response to Sunitinib.

INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.

Tsunami of immunotherapy reaches mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.

Seroprevalence and immunological memory against SARS-CoV-2 in lung cancer patients: the SOLID study.

BACKGROUND: At present, we did not find any articles that studied seroprevalence and its persistence several months later in lung cancer patients in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most patients with coronavirus disease 2019 (COVID-19) go on to develop antibodies (Abs) against viral proteins. However, it is not known how long these Abs last nor whether cancer treatments could affect the duration of immune response. METHODS: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 infection was carried out in 50 Spanish hospitals. Eligibility criterion was the diagnosis of any lung cancer. The determination of anti-SARS-CoV-2 IgG Abs was performed by qualitative immuno-enzymatic assay using enzyme-linked immunosorbent assay (ELISA) kit from NovaLisa whose Abs target the recombinant antigen N of the nucleocapsid of SARS-CoV-2. The first Ab determination was performed between April 21 and June 3, 2020. The second Ab determination was performed in all previously seropositive patients, between September 10 and November 20, 2020. Study objectives were to prospectively determine seroprevalence in unselected lung cancer patients during the first wave of the pandemic; the persistence of immunity; protection or lack thereof against reinfection; and the influence of treatments on maintenance or loss of immunity. RESULTS: Of 1,500 patients, 128 were seropositive, overall prevalence of 8.5% seropositivity [95% confidence interval (CI): 7.2-10.1%]. Seventy-five percent were in active cancer treatment. Forty-seven point seven percent of IgG positive participants had experienced a symptomatic illness suspected of being infected with SARS-CoV-2 (95% CI: 38.8-56.6%). A second determination was performed on average 4.5 months later [interquartile range (IQR), 4.0-5.0 months] and obtained for 104 of the initially seropositive patients (81%), it could not be obtained in 24 patients, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% of patients. The severity of the infection, the need for hospitalization (P=0.032) and the presence of symptoms at diagnosis (P=0.02) were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Abs loss. CONCLUSIONS: Immunity against SARS-CoV-2 does not appear to be compromised by treatment and persists beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04407143.

Thrombolytic Refusal Over Telestroke.

BACKGROUND: Tissue plasminogen activator (tPA) refusal is 4%-6% for acute ischemic stroke (AIS) in the emergency department. Telestroke (TS) has increased the use of tPA for AIS but is accompanied by barriers in communication that can affect tPA consent. We characterized the incidence of tPA refusal in our TS network and its associated reasons. METHODS: Patients with AIS who were offered tPA within 4.5 hours from symptom onset according to American Heart Association guidelines were identified within our Lone Star Stroke Consortium Telestroke Registry from September 2015 to December 2018. We compared baseline characteristics and clinical outcomes between patients who refused tPA and patients who accepted tPA. RESULTS: Among the 1,242 patients who qualified for tPA and were offered treatment, 8% refused tPA. Female and non-Hispanic Black patients and patients with a prior history of stroke were more likely to decline tPA. Patients who refused tPA presented with a lower NIHSS and were associated with a final diagnosis of stroke mimic (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.15-0.36). Good outcome (90-day modified Rankin Scale 0-2) was the same among patients who received tPA and those who refused (OR 0.80; 95% CI 0.42-1.54). The most common reasons for refusal were rapidly improving and mild/nondisabling symptoms and concern for potential side effects. CONCLUSION: tPA refusal over TS is comparable to previously reported rates; there was no difference in outcomes among patients who received tPA compared with those who refused. Sex and racial differences associated with an increased tPA refusal warrant further investigation in efforts to achieve equity/parity in tPA decisions.

Novel Tyrosine Kinase Targets in Urothelial Carcinoma.

Urothelial carcinoma represents one of the most prevalent types of cancer worldwide, and its incidence is expected to grow. Although the treatment of the advanced disease was based on chemotherapy for decades, the developments of different therapies, such as immune checkpoint inhibitors, antibody drug conjugates and tyrosine kinase inhibitors, are revolutionizing the therapeutic landscape of this tumor. This development coincides with the increasing knowledge of the pathogenesis and genetic alterations in urothelial carcinoma, from the non-muscle invasive setting to the metastatic one. The purpose of this article is to provide a comprehensive review of the different tyrosine kinase targets and their roles in the therapeutic scene of urothelial carcinoma.

Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study).

BACKGROUND: Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid. METHODS: SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression). RESULTS: Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%. CONCLUSIONS: In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.

Perfil sociodemografico de la población antioqueña en situación de desplazameinto / Socio-demographic profile of displaced population in antioquia

Este artículo recoge los principales resultados de una investigación orientada a la realización de una caracterización sociodemográfica de la población víctima del desplazamiento en Antioquia. Con el propósito de realizar un ejercicio riguroso que permitiese recoger las condiciones de vida de esta población, el equipo investigador diseñó una estrategia metodológica a partir del cruce de distintas bases de datos oficiales. Tal estrategia permitió realizar la caracterización sobre datos fiables, actualizados y verificables en mas de la tercera parte de la población.

This article contains the main results of a research oriented to the carrying out of a demographic characterization of the population victim of displacement in Antioquia. In order to carry out a rigorous exercise that would pick up the conditions of life of this population, the research team designed a methodological strategy starting from the crossing of different official databases. Such a strategy enabled the characterization of reliable, up-to-date and verifiable data on more than the third part of the population.

Estado actual de la población víctima de desplazamiento forzado en cuanto al enfoque diferencial de su atención, el derecho a la integridad, la subsistencia mínima y al ingreso económico / Current status of the population victim of forced displacement as for its differential approach of its attention, the right to integrity, the minimum sustenance and the economic income

El siguiente artículo recoge algunos aspectos de la investigación que sobre el Goce Efectivo de Derechos (Informe GED) elaborara el Observatorio Departamental de Desplazamiento Forzado de Antioquia en 2011. En esta entrega, la tercera de una serie de cuatro, se recogen algunos contenidos, metodologías de la medición, diseño de indicadores y resultados que arrojara el informe GED. En particular, en este aparte se exponen aspectos relativos a la atención de la población víctima del desplazamiento en términos del respeto a su integridad y las garantías para obtener un tratamiento acorde al enfoque diferencial. Así mismo, se tratan los diseños y resultados de la medición de los indicadores sociales sobre garantías de subsistencia mínima y alcance de la cobertura de ingresos económicos y educación en la población de estudio.

The following article contains some aspects of the research that about the effective enjoyment of rights (EER report) developed by the State Observatory of Forced Displacement in Antioquia in 2011. In this installment, the third in a series of four, the measurement methodologies, the design of indicators, and the results which the EER report will produce, are included. In particular, in this supplement, aspects relating to the care of the victims of displacement in terms of respect for their integrity and guarantees to obtain a treatment according to the differential approach. It also shows the design and the results of the measurement of the social indicators about the warranty of minimum sustenance and the scope of the coverage of the economic income and education, in the population under study.

Estado actual de los derechos a la identidad, a la vida y la vivienda en la población víctima del desplazamiento forzado en Antioquia / Current state of the rights to identity, to life, and to housing, in the population victim of forced displacement in Antioquia

El siguiente artículo es un informe de investigación que expone el diseño metodológico de una serie de indicadores que permiten establecer el estado del Goce Efectivo de Derechos (GED) de la población en situación de desplazamiento en el departamento de Antioquia. El informe GED fue realizado a partir de mandatos emanados de la Corte Constitucional colombiana en aras de la superación del estado de cosas inconstitucional de la atención de la población víctima del desplazamiento. En el artículo, el segundo de una serie de cuatro entregas, se expondrá tanto el diseño como la medición de tres indicadores: derecho a la vida, derecho a una vivienda digna y derecho a la identidad de la población estudiada.

The following article is a research report that exposes the methodological design in a series of indicators that allow you to set the state of the Effective Enjoyment of Rights (EER) of the population in situation of displacement in the State of Antioquia. The EER report was made from mandates arising from the Colombian Constitutional Court in the interest of the overcoming of the unconstitutional state of affairs for the attention of the population victim of displacement. In the article, the second in a series of four issues, both the design and the measurement of three indicators will be exposed: right to life, the right to decent housing, and right to identity of the studied population.

Población en situación de desplazamiento en antioquia: El papel del enfoque de derechos en los aspectos técnicos para el diseño y medición de indicadores: (parte 1) / Population in situation of displacement in antioquia: The role of the approach of rights in the technical aspects for the design and the measurement of indicators: (part 1)

Este artículo, expone los resultados y lineamientos metodológicos derivados de una investigación realizada por el Observatorio Departamental de Desplazamiento Forzado de Antioquia (ODDIF) para estimar el estado del Goce Efectivo de Derechos (GED) de la población víctima de desplazamiento forzado en el Departamento. Esta investigación fue realizada en respuesta a los Autos de Seguimiento y a las órdenes impartidas en la sentencia T-025 de 2004 de la Corte Constitucional. El Auto 116 de 2008, estableció los parámetros de medición a adoptar por parte de los entes territoriales para rendir cuentas sobre la garantía de los derechos de esta población. Con el objeto de ofrecer elementos de análisis tanto para las instituciones como para las organizaciones de la sociedad civil, tanto nacionales como internacionales, que analizan y siguen el comportamiento de las situación socioeconómica de las víctimas del conflicto armado en Colombia, en una serie de cuatro artículos, se cubrirán tanto la metodología de medición como algunos de los resultados hallados en el GED de Antioquia. En esta entrega, en particular, serán expuestos el marco normativo del informe, el enfoque teórico de los indicadores tratados y las principales consideraciones técnicas y metodológicas para su medición. A manera de resultado de investigación, en esta entrega del informe se señala las diferencias -tanto en las metodologías como en las cifras- que hay en la medición de la situación sociooeconómica de la población en situación de desplazamiento realizada por el DNP y la medición de esta realizada por el Observatorio

This article introduces the results and the methodological guidelines derived from a piece of research carried out by the State Observatory of Forced Displacement in Antioquia (ODDIF), in order to estimate the state of Full Possession of Rights of the population victim of forced displacement in the State of Antioquia. This piece of research was carried out as a response to the Proceedings of Follow-up and the orders given in the sentence T-025 as of 2004 of the Constitutional Court. The Proceeding 116 of 2008 established the parameters of measurement to be adopted by the territorial entities, in order to render accounts about the guarantee of the rights of such a population. With the object of offering elements of analysis both for the institutions and the organizations of the civil society, both national and international ones, which analyze and follow the behavior of the socio-economic situation of the victims of the armed conflict in Colombia, in a series of four articles, the methodology of measurement and some results found in the Full Possession of Rights in Antioquia will be covered. In this issue, in particular, the normative framework of the report, the theoretical approach of the indicators treated and the main technical and methodological considerations for their measurement will be exposed. By way of result of research, in this issue, both methodological and figure differences, which are used for the measurement of the socio-economic situation of the population who is in a situation of displacement carried out by the National Planning Department and its measurement carried out by the Observatory, are established