Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial.

Abstract Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs. Keywords: NGS; circulating free DNA; epidermal growth factor receptor; non-small-cell lung cancer; osimertinib; tyrosine kinase inhibitor

Características psicossociais e familiares relacionadas à tentativa de suicídio em uma população adolescente em Bogotá (2009)

Suicidal behavior has become a major cause of morbidity and mortality worldwide. In 2006, it was the third leading cause of death among persons age 15 to 44. Risk factors for this behavior and specific warning signs have been identified. However, adolescents may be plagued by additional risk factors such as imitation, social identification, and emotional instability.The authors conducted a transversal- descriptive study with adolescents between 10 and 17 years of age who were admitted for attempted suicide to the emergency rooms of two hospitals in Bogota. The data was collected with an instrument filled out by the parents or guardians of 14 different patients, after having signed a letter giving informed consent. The study showed the most prevalent age was 16, accounting for 43% of the sample. The female population was the most prevalent in terms of gender, accounting for 71.5%. None of the patients reported a previous diagnosis of mental illness and, in only three specific cases, was there a report of substance abuse. None of the patients reported having sought help prior to attempting suicide.Due to the small number of cases in the sample, it is possible only to describe the reported findings. At this point, conclusions cannot be reached with respect to family characteristics. To do so would require applying the instrument to a larger sample of patients.DOI: 10.5294/pebi.2010.14.2.8 Las conductas suicidas se han constituido en una causa importante de morbi-mortalidad mundial. En el 2006, el suicidio pasó al tercer lugar como principal causa de muerte en personas de 15 a 44 años. Se han identificado factores de riesgo para esta conducta y signos de alarma específicos, sin embargo, los adolescentes presentan riesgos adicionales como imitación, identificación social e inestabilidad emocional.Se realizó un estudio transversal descriptivo en adolescentes entre los 10 y 17 años que consultaron por intento de suicidio al servicio de urgencias de dos hospitales en Bogotá, aplicando un instrumento de recolección de información diligenciado por los padres o acudientes de 14 casos, previa firma de consentimiento informado. El estudió mostró que la edad más prevalente fueron los 16 años, representando el 43%; el género fue el femenino, representando el 71,5%. Ninguno reportó diagnóstico de enfermedad mental previa, y solo en tres casos hubo reporte de consumo de sustancias.Ninguno de los casos reportó que los pacientes hubieran tenido comportamientos de búsqueda de ayuda previa.Debido al reducido número de casos sólo se pueden describir hallazgos reportados, en este momento no se pueden hacer afirmaciones con respecto a características familiares, para esto se requeriría aplicar el instrumento en un mayor número de pacientes. DOI: 10.5294/pebi.2010.14.2.8Os comportamentos suicidas têm se tornado uma das principais causas de morbidade e mortalidade no mundo. Em 2006, o suicídio foi a terceira causa principal de morte em pessoas entre 15 e 44 anos. Para este comportamento identificaram-se fatores de risco e sinais de advertência. Existem otros riscos para os adolescentes: a imitação, a identificação social e a instabilidade emocional.Foi realizado um estudo transversal descritivo em adolescentes de 10 a 17 anos que consultaram o departamento de emergência de dois hospitais de Bogotá por tentativa de suicídio. Utilizou-se um instrumento de coleta de dados preenchidos pelos pais ou responsáveis dos adolescentes em 14 casos, após a assinatura de um consentimento informado. O estudo mostrou que a faixa etária prevalente é 16 anos (43%), o sexo foi o feminino (71,5%). Nenhum caso relata diagnóstico prévio de doença mental, e apenas três casos relataram o uso de substâncias.Nenhum dos casos informou que os pacientes tenham procurado ajuda previa.Devido ao pequeno número de casos, só podem descrever-se achados relatados. Neste momento, nós não podemos fazer afirmações sobre as características da família, já que seria necessária a aplicação do instrumento em um número maior de pacientes

Características psicosociales y familiares relacionadas con intento de suicidio en una población adolescente en Bogotá-2009

Suicidal behavior has become a major cause of morbidity and mortality worldwide. In 2006, it was the third leading cause of death among persons age 15 to 44. Risk factors for this behavior and specific warning signs have been identified. However, adolescents may be plagued by additional risk factors such as imitation, social identification, and emotional instability. The authors conducted a transversal- descriptive study with adolescents between 10 and 17 years of age who were admitted for attempted suicide to the emergency rooms of two hospitals in Bogota. The data was collected with an instrument filled out by the parents or guardians of 14 different patients, after having signed a letter giving informed consent. The study showed the most prevalent age was 16, accounting for 43% of the sample. The female population was the most prevalent in terms of gender, accounting for 71.5%. None of the patients reported a previous diagnosis of mental illness and, in only three specific cases, was there a report of substance abuse. None of the patients reported having sought help prior to attempting suicide. Due to the small number of cases in the sample, it is possible only to describe the reported findings. At this point, conclusions cannot be reached with respect to family characteristics. To do so would require applying the instrument to a larger sample of patients.Os comportamentos suicidas têm se tornado uma das principais causas de morbidade e mortalidade no mundo. Em 2006, o suicídio foi a terceira causa principal de morte em pessoas entre 15 e 44 anos. Para este comportamento identificaram-se fatores de risco e sinais de advertência. Existem otros riscos para os adolescentes: a imitação, a identificação social e a instabilidade emocional. Foi realizado um estudo transversal descritivo em adolescentes de 10 a 17 anos que consultaram o departamento de emergência de dois hospitais de Bogotá por tentativa de suicídio. Utilizou-se um instrumento de coleta de dados preenchidos pelos pais ou responsáveis dos adolescentes em 14 casos, após a assinatura de um consentimento informado. O estudo mostrou que a faixa etária prevalente é 16 anos (43%), o sexo foi o feminino (71,5%). Nenhum caso relata diagnóstico prévio de doença mental, e apenas três casos relataram o uso de substâncias. Nenhum dos casos informou que os pacientes tenham procurado ajuda previa. Devido ao pequeno número de casos, só podem descrever-se achados relatados. Neste momento, nós não podemos fazer afirmações sobre as características da família, já que seria necessária a aplicação do instrumento em um número maior de pacientes.Las conductas suicidas se han constituido en una causa importante de morbi-mortalidad mundial. En el 2006, el suicidio pasó al tercer lugar como principal causa de muerte en personas de 15 a 44 años. Se han identificado factores de riesgo para esta conducta y signos de alarma específicos, sin embargo, los adolescentes presentan riesgos adicionales como imitación, identificación social e inestabilidad emocional. Se realizó un estudio transversal descriptivo en adolescentes entre los 10 y 17 años que consultaron por intento de suicidio al servicio de urgencias de dos hospitales en Bogotá, aplicando un instrumento de recolección de información diligenciado por los padres o acudientes de 14 casos, previa firma de consentimiento informado. El estudió mostró que la edad más prevalente fueron los 16 años, representando el 43%; el género fue el femenino, representando el 71,5%. Ninguno reportó diagnóstico de enfermedad mental previa, y solo en tres casos hubo reporte de consumo de sustancias. Ninguno de los casos reportó que los pacientes hubieran tenido comportamientos de búsqueda de ayuda previa. Debido al reducido número de casos sólo se pueden describir hallazgos reportados, en este momento no se pueden hacer afirmaciones con respecto a características familiares, para esto se requeriría aplicar el instrumento en un mayor número de pacientes

Características psicosociales y familiares relacionadas con intentos de suicidio en una población adolescente en Bogotá-2009

6 páginasSuicidal behavior has become a major cause of morbidity and mortality worldwide. In 2006, it was the third leading cause of death among persons age 15 to 44. Risk factors for this behavior and specific warning signs have been identified. However, adolescents may be plagued by additional risk factors such as imitation, social identification, and emotional instability. The authors conducted a transversal- descriptive study with adolescents between 10 and 17 years of age who were admitted for attempted suicide to the emergency rooms of two hospitals in Bogota. The data was collected with an instrument filled out by the parents or guardians of 14 different patients, after having signed a letter giving informed consent. The study showed the most prevalent age was 16, accounting for 43% of the sample. The female population was the most prevalent in terms of gender, accounting for 71.5%. None of the patients reported a previous diagnosis of mental illness and, in only three specific cases, was there a report of substance abuse. None of the patients reported having sought help prior to attempting suicide. Due to the small number of cases in the sample, it is possible only to describe the reported findings. At this point, conclusions cannot be reached with respect to family characteristics. To do so would require applying the instrument to a larger sample of patients.Las conductas suicidas se han constituido en una causa importante de morbi-mortalidad mundial. En el 2006, el suicidio pasó al tercer lugar como principal causa de muerte en personas de 15 a 44 años. Se han identificado factores de riesgo para esta conducta y signos de alarma específicos, sin embargo, los adolescentes presentan riesgos adicionales como imitación, identificación social e inestabilidad emocional. Se realizó un estudio transversal descriptivo en adolescentes entre los 10 y 17 años que consultaron por intento de suicidio al servicio de urgencias de dos hospitales en Bogotá, aplicando un instrumento de recolección de información diligenciado por los padres o acudientes de 14 casos, previa firma de consentimiento informado. El estudió mostró que la edad más prevalente fueron los 16 años, representando el 43%; el género fue el femenino, representando el 71,5%. Ninguno reportó diagnóstico de enfermedad mental previa, y solo en tres casos hubo reporte de consumo de sustancias. Ninguno de los casos reportó que los pacientes hubieran tenido comportamientos de búsqueda de ayuda previa. Debido al reducido número de casos sólo se pueden describir hallazgos reportados, en este momento no se pueden hacer afirmaciones con respecto a características familiares, para esto se requeriría aplicar el instrumento en un mayor número de pacientes

Diversidad florística en playas de la región Archipiélagos del Sur de Cuba

Based on the implementation results of the Monitoring Program of the sandy coastal vegetation complex in the archipelagoes of South Cuba region as part of the GEF-UNDP project "Implementation of a regional approach to coastal and marine management in protected areas in the region of the archipelagoes of south Cuba", during the years 2011 to 2013, an analysis is presented particularized on floristic diversity found in the three national parks included in the program (Guanahacabibes, Cayos de San Felipe and Jardines de la Reina). In total were measured by the 14 permanent plots established, 0.14 hectares of seven beaches. The results show that all the beaches have their differentiation in terms of biodiversity, basically due to the heterogeneity observed, being Guanahacabibes the most diverse park; this variable is attenuated in an eastern direction, with lower registers is Jardines de la Reina. The affinities analysis enabled confirm greater similarities between the beaches of each one of the protected areas, differentiating in terms of the presence - absence of species to each one of the National Parks evaluated.A partir de los resultados de la aplicación del Programa de Monitoreo del complejo de vegetación de costa arenosa en la región de los archipiélagos del sur de Cuba como parte del proyecto GEF-PNUD “Aplicación de un enfoque regional al manejo de áreas costeras y marinas protegidas en la región de los archipiélagos del sur de Cuba”, durante los años 2011 a 2013, se presenta un análisis particularizado sobre la diversidad florística encontrada en los tres Parques Nacionales incluidos en el programa (Guanahacabibes, Cayos de San Felipe y Jardines de la Reina). En total se midieron mediante las 14 parcelas permanentes establecidas, 0.14 hectáreas de siete playas. Los resultados muestran que todas las playas poseen su diferenciación en cuanto a diversidad, básicamente por la heterogeneidad observada, siendo Guanahacabibes la más diversa; esta variable se atenúa en dirección hacia el este, con registros inferiores es Jardines de la Reina. El análisis de afinidades realizado posibilitó confirmar mayores similitudes entre las playas de cada una de las áreas protegidas, diferenciando en cuanto a la presencia-ausencia de especies a cada uno de los Parques Nacionales evaluados

Niveles plasmáticos de triptófano en pacientes cubanos con esquizofrenia

Introduction. Schizophrenia is a heterogeneous psychiatric disorder that affects 1% of the world's population. The pathophysiology of this disease has been reported to be involved with several neurotransmitter systems, such as serotonin. Because serotonin synthesis depends on the availability of tryptophan, we studied plasma tryptophan levels in Cuban patients with schizophrenia. Objective. To determine plasma concentrations of tryptophan in patients with schizophrenia. Materials and Methods. A descriptive crosssectional study was performed. The sample consisted of 400 patients treated at the Psychiatric Hospital of Havana with clinical diagnoses of schizophrenia. Patient's psychopathological assessment were completed using Schedules for Clinical Assessment in Neuropsychiatry (SCAN) protocols. The reference population group comprised 157 apparently healthy individuals of both sexes. Plasma tryptophan levels were quantified by HPLC. Results. A significant decrease in plasma tryptophan concentrations (p = 0,0001) were observed as related to the sex of the patient, with the female patients presenting the lowest values of tryptophan compared to reference values. It was observed that patients with concentrations below 370 μM tryptophan, had the most severe degrees of SCAN as evaluated by clinical variables related to negative symptoms with schizophreniform speech abnormalities (64.3%) and negative syndrome (61.8%). Conclusion. Patients with schizophrenia with low concentrations of tryptophan may have alterations in their serotonergic systems, which could explain the severity observed in relation to the negative symptoms of the disease and could also point to candidates in the search for genes associated with serotonin pathways. Based on these findings, it is recommended that the measurement of plasma tryptophan concentrations should be considered when selecting therapies for treating schizophrenia.Introducción. La esquizofrenia es un trastorno psiquiátrico muy heterogéneo, que afecta el 1 % de la población mundial. Se ha descrito que en la patofisiología de esta enfermedad pueden estar implicados varios sistemas de neurotransmisores, como el serotoninérgico. La síntesis de la serotonina depende de la disponibilidad de triptófano. Objetivo. Determinar las concentraciones plasmáticas de triptófano en pacientes con esquizofrenia. Materiales y Métodos. Se realizó un estudio descriptivo de tipo transversal. La muestra estuvo conformada por 400 pacientes atendidos en el Hospital Psiquiátrico de La Habana con diagnóstico clínico de esquizofrenia. Para realizar la evaluación psicopatológica de los pacientes se aplicó el cuestionario de evaluación clínica en neuropsiquiatría (SCAN). Se utilizó como población de referencia un grupo conformado por 157 individuos de ambos sexos, aparentemente sanos. Los niveles de triptófano en plasma fueron cuantificados mediante HPLC. Resultados. Se apreció una disminución significativa en las concentraciones de triptófano (p=0,0001) atendiendo al sexo; las personas del sexo femenino presentaron los valores más bajos del triptófano en comparación con los valores de referencia. Se observó que los pacientes con concentraciones de triptófano inferiores a 370 μM presentaban los grados más severos de las variables clínicas evaluadas mediante el SCAN, relacionadas con los síntomas negativos: anormalidades esquizofreniformes del lenguaje (64.3%) y síndrome negativo (61.8%). Conclusión. Los pacientes con esquizofrenia con bajas concentraciones de triptófano podrían presentar alteraciones en el sistema serotoninérgico, lo cual podría explicar la severidad observada en relación con los síntomas negativos de la enfermedad y serían candidatos para la búsqueda de genes relacionados con la vía de la serotonina. De acuerdo con estos hallazgos, se recomienda que la medición de las concentraciones de triptófano debiera ser un aspecto para tener en cuenta en la selección de la terapia por utilizar en esta enfermedad

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

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. 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. 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. 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. ClinicalTrials.gov identifier: NCT04407143

Are there differences by sex in lung cancer characteristics at diagnosis? -a nationwide study

Background: Lung cancer causes approximately 25% of all cancer deaths. Despite its relevance, few studies have analyzed differences by sex at the time of diagnosis in terms of symptoms, stage, age or smoking status. We aim to assess if there are differences between men and women on these characteristics at diagnosis. Methods: We analyzed the Thoracic Tumour Registry (TTR), sponsored by the Spanish Lung Cancer Group using a case-series design. This is a nationwide registry of lung cancer cases which started recruitment in 2016. For each case included, clinicians fulfilled an electronic record registering demographic data, symptoms, exposure to lung cancer risk factors, and treatment received in detail. We compared men and women using descriptive statistics. Results: A total of 13,590 participants took part in this study, 25.6% women. Women were 4 years younger than men (64 vs. 69), and men had smoked more frequently. Adenocarcinoma was the most frequent histological type in both sexes. Stage IV at diagnosis was 50.8% in women compared to 43.6% in men. Weight loss/anorexia/asthenia was the most frequent symptom in both sexes and there were no differences in the number of symptoms at diagnosis. There were no relevant differences in the frequency or number of symptoms by sex when non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were analyzed separately. Smoking status did not appear to cause different lung cancer presentation in men compared to women.This research received funding from the Spanish Lung Cancer GroupYe

Prognostic model of long-term advanced stage (IIIB-IV) EGFR mutated non-small cell lung cancer (NSCLC) survivors using real-life data.

There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0-1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients