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RESUMEN Objetivo: Los pacientes con cáncer de pulmón de células no pequeñas positivas a la mutación del gen linfoma anaplásico quinasa (ALK+) que, además, presentan mutaciones en el gen Kirsten rat sarcoma (KRAS), como KRASG12C, están mostrando resistencia tanto a inhibidores del gen linfoma anaplásico quinasa (ALK) como de KRAS. Por ello, se analizó la interacción de los inhibidores de ALK con KRAS, para sugerir una sinergia entre ambos. Materiales y métodos: En el estudio se realizó un modelado por homología de las estructuras KRASwt, KRASG12C y ALKwt. Posteriormente, se realizaron acoplamientos moleculares para determinar la energía de unión de los inhibidores de ALK y de KRAS, y evaluar la posible interacción entre los inhibidores de ALK con KRAS y la estructura KRASG12C. Finalmente, se analizó la expresión en la vía de proliferación celular de las proteínas rat sarcoma/quinasa regulada por señales extracelulares (vía RAS/MEK) mediante la técnica de Western blot. Resultados: Los valores de energía de unión muestran la posibilidad de interacción de los inhibidores de ALKwt, como crizotinib y alectinib, con las estructuras de KRASwt y KRASG12C. Los acoplamientos entre crizotinib con KRASwt y KRASG12C, respectivamente, muestran valores de energía de interacción (42,77 kcal/mol y 46,20 kcal/mol) muy similares a los obtenidos entre crizotinib y ALK (42,37 kcal/mol). A su vez, alectinib se acopló en el mismo sitio que los fármacos específicos de KRAS y KRASG12C, y presentaron valores de energía de interacción (51,74 kcal/mol y 54,69 kcal/mol, respectivamente) superiores a los obtenidos con ALK (44,94 kcal/mol). Finalmente, la expresión de la vía RAS/MEK nos mostró una disminución significativa de la expresión de RAS en líneas celulares de cáncer de pulmón ALK+ y ALKL1196M tratadas con crizotinib y alectinib. Conclusiones: Las técnicas in silico de este estudio muestran la posibilidad de acoplamiento entre los inhibidores de ALK (crizotinib y alectinib) con la estructura de KRAS. Esto permite sugerir una posible terapia combinada entre inhibidores de KRAS y ALK para los casos de coexistencia de ambas mutaciones, que puede evaluarse en posteriores ensayos con líneas celulares.
ABSTRACT Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as crizotinib and alectinib, with the KRASwt and KRAS G12C structures. The binding of crizotinib to KRASwt and KRAS G12C, respectively, indicates interaction energy values (42.77 kcal/mol and 46.20 kcal/mol) which are very similar to those obtained between crizotinib and ALK (42.37 kcal/mol). In turn, alectinib bound to the same site as drugs targeting KRAS and KRAS G12C, and showed interaction energy values (51.74 kcal/mol and 54.69 kcal/mol, respectively) higher than those obtained with ALK (44.94 kcal/mol). Finally, a significant decrease in RAS expression within the RAS/MEK pathway was observed in ALK+ and ALK 1196M lung cancer cell lines treated with crizotinib and alectinib. Conclusions: In silico techniques of this study demonstrate the potential binding of ALK inhibitors (crizotinib and alectinib) to the KRAS structure. In addition, this allows suggesting a possible combined therapy between KRAS and ALK inhibitors for cases of coexistence of both mutations that can be assessed in subsequent trials with cell lines.
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RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.
ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.
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El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.
Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.
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La estadificación ganglionar mediastínica es crucial en el diagnóstico, pronóstico y tratamiento del cáncer de pulmón. Si no existe enfermedad metastásica a distancia, la decisión terapéutica depende de la afectación ganglionar mediastínica. Existen distintas técnicas quirúrgicas dependiendo del tamaño, lateralidad y localización de las adenopatías, así como del tumor primitivo. (AU)
Mediastinal lymph node staging is crucial in the diagnosis, prognosis, and treatment of lung cancer. If there is no distant metastatic disease, the therapeutic decision depends on mediastinal lymph node involvement. There are different surgical techniques depending on the size, laterality and location of the adenopathies, as well as the primitive tumor. (AU)
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Humanos , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estadificación de Neoplasias , LinfadenopatíaRESUMEN
OBJECTIVE: To compare the diagnostic performance of 18F-FDG PET/MR and PET/CT preliminarily for the thoracic staging of non-small cell lung cancer (NSCLC) with a special focus on pleural invasion evaluation. METHODS: 52 patients with pathologically confirmed NSCLC were included and followed for another year. Whole-body 18F-FDG PET/CT and subsequent thoracic PET/MR were performed for initial thoracic staging. Thoracic (simultaneous) PET/MR acquired PET images and MRI sequences including T2 weighted imaging, with and without fat saturation, T1 weighted imaging, and diffusion weighted imaging (DWI). Two radiologists independently assessed the thoracic T, N staging and pleural involvement. The McNemar Chi-square test was used to compare the differences between PET/CT and PET/MR in the criteria. The area under the receiver-operating-characteristic curves (AUC) was calculated. RESULTS: Compared to PET/CT, PET/MR exhibited higher sensitivity, specificity in the detection of pleural invasion; 82 % vs. 64% (pâ¯=â¯0.625), 98 % vs. 95% (pâ¯=â¯1.000), PET/MR to PET/CT respectively. The receiver-operating-characteristic analysis results of PET/CT vs PET/MR for the pleural invasion were as follow: AUCPET/CTâ¯=â¯0.79, AUCPET/MRâ¯=â¯0.90, pâ¯=â¯0.21. Both T staging results and N staging results were approximately identical in PET/CT and PET/MR. Differences between PET/CT and PET/MR in T staging, N staging as well as pleural invasion accuracy were not statistically significant (pâ¯>â¯0.05, each). CONCLUSION: PET/MR and PET/CT demonstrated equivalent performance about the evaluation of preoperative thoracic staging of NSCLC patients. PET/MR may have greater potential in pleural invasion evaluation for NSCLC, especially for solid nodules, crucial to clinical decision-making, though our results did not demonstrate statistical significance.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Estadificación de Neoplasias , Imagen por Resonancia MagnéticaRESUMEN
RESUMEN Introducción: el cáncer de pulmón tiene elevada incidencia a nivel mundial. En cuanto a mortalidad, es la primera localización en ambos sexos, con una tasa de 58,0 por 100 000 y 32,5 por 100 000 en el año 2017 en hombre y mujeres respectivamente. Objetivos: identificar los factores relacionados con la supervivencia de los pacientes con cáncer de pulmón de células no pequeñas. Métodos: se realizó un estudio analítico y observacional de cohorte en pacientes atendidos con el diagnóstico de cáncer de pulmón de células no pequeñas en el servicio de Oncología de del hospital general universitario "Carlos Manuel de Céspedes" de Bayamo, Granma, en el período comprendido desde el 1º de enero del 2014 al 31 de diciembre de 2019. Resultados: el factor más relevante y de carácter independiente fue clasificar en estadio IV al incrementar el riesgo de morir a 1,304 veces (IC: 1,011-2,025; p: 0,000) seguido del estadio IIIB (HR: 1,070; IC: 1,004-2,113; p: 0,000). El modelo de regresión de Cox tiene una capacidad discriminativa adecuada para predecir los pacientes que fallecerán de los que no en pacientes con cáncer de pulmón de células no pequeñas (área: 0,727; IC: 0,516-0,737; p: 0,025). Conclusiones: el estadio del cáncer de pulmón de células no pequeñas tuvo una relación inversamente proporcional con la sobrevida de los pacientes; la edad avanzada incrementó el riesgo de morir. El modelo de regresión proporcional de Cox tuvo una capacidad discriminativa adecuada para precisar la menor supervivencia de los pacientes con el mencionado diagnóstico.
ABSTRACT Introduction: lung cancer has a high incidence worldwide. In terms of mortality, it is the first location in both sexes, with a rate of 58.0 per 100,000 and 32.5 per 100,000 in 2017 in men and women respectively. Objectives: to identify factors related to the survival of patients with non-small cell lung cancer. Methods: an analytical and observational cohort study was conducted in patients treated with the diagnosis of non-small cell lung cancer in the Oncology service of the "Carlos Manuel de Céspedes" general university hospital in Bayamo, Granma, in the period from January 1, 2014 to December 31, 2019. Results: the most relevant and independent factor was to classify in stage IV by increasing the risk of dying to 1,304 times (CI: 1.011-2.025; p: 0.000) followed by stage IIIB (HR: 1.070; CI: 1.004-2.113; p: 0.000). The Cox regression model has an adequate discriminative capacity to predict patients who will die from those who will not in patients with non-small cell lung cancer (area: 0.727; CI: 0.516-0.737; p: 0.025). Conclusions: the stage of non-small cell lung cancer had an inversely proportional relationship with the survival of patients; older age increased the risk of dying. The Cox proportional regression model had an adequate discriminative capacity to specify the shortest survival of patients with the aforementioned diagnosis.
RESUMO Introdução: o câncer de pulmãot em alta incidência em todo o mundo. Em termos de mortalidade, é a primeira localização em ambos os sexos, comum ataxa de 58,0 por 100.000 e 32,5 por 100.000 em 2017 em homens e mulheres, respectivamente. Objetivos: identificar fatores relacionados à sobrevivência de pacientes com câncer de pulmão de células não pequenas. Métodos: estudo de coorte analítica e observacional foi realizado em pacientes tratados com o diagnóstico de câncer de pulmão de células não pequenas no serviço de Oncologia do Hospital Universitário Geral Carlos Manuel de Céspedes, em Bayamo, Granma, no período de 1º de janeiro de 2014 a 31 de dezembro de 2019. Resultados: o fator mais relevante e independente foi classificar na fase IV o aumento do risco de morrer para 1.304 vezes (IC: 1.011-2.025; p: 0,000) seguido da etapa IIIB (HR: 1.070; CI: 1.004-2.113; p: 0,000). O modelo de regressão de Cox tem uma capacidade discriminatória adequada para prever pacientes que morrerão daqueles que não morrerão em pacientes com câncer de pulmão de células não pequenas (área: 0,727; CI: 0.516-0.737; p: 0,025). Conclusões: o estágio do câncer de pulmão de células não pequenas teve uma relação inversamente proporcional com a sobrevivência dos pacientes; a idade mais velha aumentou o risco de morrer. O modelo de regressão proporcional de Cox apresentou capacidade discriminatória adequada para especificar a menor sobrevida dos pacientes com o diagnóstico acima mencionado.
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Introduction: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers.Methods: A multicentre, hospital-based, casecontrol study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants dwellings.Results: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.445.2) and heavy smokers (OR 3.04; 95%CI 1.217.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.6458.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.158.48).Conclusion: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent. (AU)
Introducción: El consumo de tabaco y la exposición al radón se consideran la primera y la segunda causa más frecuentes de cáncer de pulmón, respectivamente. El objetivo de este estudio fue analizar si determinados polimorfismos genéticos en los loci que forman parte de la cascada de reparación del ADN se asocian con el cáncer de pulmón de célula no pequeña, y también si es posible que modifiquen la asociación entre la exposición al radón en el hogar y el cáncer de pulmón tanto en fumadores como en no fumadores.Métodos: Se diseñó un estudio multicéntrico hospitalario de casos y controles con 826 casos y 1.201 controles en un área proclive a la presencia de radón. Se determinó el genotipo en sangre y se midió la exposición al radón en el lugar de residencia de los participantes.Resultados: Analizando la exposición al tabaco, la variante del gen NBN (rs1805794) se asoció con el cáncer de pulmón en no fumadores (OR 2,72; IC 95% 1,44-5,2) y grandes fumadores (OR 3,04; IC 95% 1,21-7,69). El polimorfismo con mayor asociación con el cáncer de pulmón fue OGG1 (rs125701), con una OR de 8,04 (IC 95% 1,64-58,29) para la variante genotípica en homocigosis en grandes fumadores. En cuanto a la exposición al radón en interiores (>200Bq/m3), rs1452584 en homocigosis mostró la asociación más fuerte (OR 3,04; IC 95% 1,15-8,48).Conclusión: Los genes que se analizaron no muestran asociación con el modelo completamente ajustado, pero podrían modificar la asociación con el cáncer de pulmón cuando se consideran diferentes categorías de consumo de tabaco (esto es, grandes fumadores). Esta asociación podría aumentar de forma similar en aquellos individuos que están expuestos al radón en interiores, aunque en menor medida. (AU)
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Humanos , Contaminación por Humo de Tabaco , Radón , Neoplasias Pulmonares , No Fumadores , GenesRESUMEN
RESUMEN Introducción: el cáncer de pulmón representa en el mundo la primera causa de muerte oncológica. La tomografía computarizada es el medio diagnóstico más utilizado para clasificar esta enfermedad por estadios. Objetivo: determinar la eficacia de la tomografía computarizada en la evaluación de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana. Materiales y métodos: se realizó un estudio de evaluación, longitudinal, retrospectivo, analítico, en pacientes con cáncer de pulmón de células no pequeñas en estadio avanzado, tratados con inmunoterapia activa cubana, después de la primera línea de tratamiento con quimioterapia o quimiorradioterapia, entre el 1 de enero de 2013 y el 31 de diciembre de 2017. El universo lo constituyeron 91 pacientes tratados con Racotumomab y CIMAvax-EGF. Los datos se obtuvieron de las historias clínicas individuales, se incorporaron en una base de datos en Excel y se analizaron estadísticamente con el paquete SPSS 23. Resultados: del total de pacientes, 28 recibieron la vacuna Racotumomab y 63 la CIMAvax-EGF: pseudoprogresó el 12,5 % de los tratados con Racotumomab y el 28 % de los que lo fueron con CIMAvax-EGF. Se observó que la mayor supervivencia fue en los pseudoprogresores. Conclusiones: es eficaz el estudio tomográfico en la evaluación de respuesta de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana.
ABSTRACT Introduction: lung cancer represents the first cause of oncological death in the world. Computed tomography is the most used diagnostic mean to classify the disease by stages. Objective: to determine the efficacy of computed tomography in the evaluation of the disease pseudo-progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy. Materials and methods: a longitudinal, retrospective, analytical study was conducted in patients with non-small cells lung cancer in advanced stage, treated with Cuban active immunotherapy after the first line of treatment with chemotherapy and chemoradiotherapy, between January 1, 2013 and December 31, 2017. The universe were 91 patients treated with Racotumomab and CIMAvax-EGF. Data were collected from personal clinical records, incorporated in an Excel database and statistically analyzed with the SPSS 23 package. Results: 28 patients from the total received the Racotumomab vaccine and 63 received the CIMAvax-ECG vaccine. 12.5 % of those treated with Racotumomab and 28 % of those treated with CIMAvax-ECG pseudo progressed. The greatest survival was found in pseudo progressors. Conclusions: the computed tomographic studio is efficacious in evaluating the response of the disease pseudo progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy.
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INTRODUCTION: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. METHODS: A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings. RESULTS: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48). CONCLUSION: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.
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Contaminación del Aire Interior , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Inducidas por Radiación , Radón , Contaminación del Aire Interior/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/etiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios de Casos y Controles , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Neoplasias Inducidas por Radiación/etiología , Polimorfismo Genético , Radón/efectos adversos , Factores de Riesgo , NicotianaRESUMEN
RESUMEN Introducción: El cáncer de pulmón está afectando cada vez más a la población de adultos mayores, a medida que la expectativa de vida aumenta. Sin embargo, es difícil establecer la eficacia de la quimioterapia y el pronóstico de estos pacientes es grave. Objetivo: Presentar un caso de paciente adulto mayor con cáncer de pulmón avanzado de células no pequeñas, con una prolongada sobrevida que recibió solamente quimioterapia de primera línea. Caso clínico: Paciente no fumador, de 71 años, diagnosticado con cáncer de pulmón de células no pequeñas avanzado, del subtipo adenocarcinoma, con compromiso pleural. Inició tratamiento con carboplatino 5 AUC y gemcitabina 1,1 g. En el noveno ciclo, se encontró reducción de los nódulos pulmonares, pero también metástasis en el nivel D6-D7. Inició la segunda línea de tratamiento con carboplatino 5,4 AUC, paclitaxel 200 mg y ácido zolendrónico en dosis de 4,0 mg. Debido a eventos adversos, el tratamiento fue cambiado a vinorelbina 2,5 g y ácido zolendrónico 4,0 mg. Tras dos ciclos, el paciente fallece, alcanzando 21 meses de sobrevida global, solo con quimioterapia. Conclusión: El tratamiento del paciente adulto mayor con cáncer de pulmón es complejo. En el presente esquema de quimioterapia, el paciente pudo alcanzar 21 meses de sobrevida global, a pesar de que no fue caracterizado molecularmente.
ABSTRACT Introduction: Lung cancer is taking an increasing toll on the older population as life expectancy increases. However, the efficacy of chemotherapy is difficult to establish and the prognosis of these patients is severe. Objective: Report a case of an older adult patient with advanced non-small cell lung cancer with prolonged survival who received only first-line chemotherapy. Case report: A 71-year-old non-smoker patient diagnosed with advanced non-small cell lung cancer, adenocarcinoma subtype, with pleural involvement. He started treatment with carboplatin 5 AUC and gemcitabine 1,1 g. In the ninth cycle, reduction of pulmonary nodules was found, but he also had metastases at the D6-D7 level. He started the second line of treatment with carboplatin 5,4 AUC, paclitaxel 200 mg and zolendronic acid at a dose of 4,0 mg. Due to adverse events, the treatment was changed to vinorelbine 2,5 g and zolendronic acid 4.0 mg. After two cycles, the patient died, reaching 21 months of overall survival, only with chemotherapy. Conclusion: The treatment of the older adult patient with lung cancer is challenging. In the present chemotherapy treatment, the patient was able to achieve 21 months of overall survival, despite the fact that he was not molecularly characterized.
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PURPOSE: The aims of this study were to evaluate the relationships between textural features of the primary tumor on FDG PET images and clinical-histopathological parameters which are useful in predicting prognosis in newly diagnosed non-small cell lung cancer (NSCLC) patients. METHODS: PET/CT images of ninety (90) patients with NSCLC prior to surgery were analyzed retrospectively. All patients had resectable tumors. From the images we acquired data related to metabolism (SUVmax, MTV, TLG) and texture features of primary tumors. Histopathological tumor types and subgroups, degree of Ki-67 expression and necrosis rates of the primary tumor, mediastinal lymph node (MLN) status and nodal stages were recorded. RESULTS: Among the two histologic tumor types (adenocarcinoma and squamous cell carcinoma) significant differences were present regarding metabolic parameters, Ki-67 index with higher values and kurtosis with lower values in the latter group. Textural heterogeneity was found to be higher in poorly differentiated tumors compared to moderately differentiated tumors in patients with adenocarcinoma. While Ki-67 index had significant correlations with metabolic parameters and kurtosis, tumor necrosis rate was only significantly correlated with textural features. By univariate and multivariate analyses of the imaging and histopathological factors examined, only gradient variance was significant predictive factor for the presence of MLN metastasis. CONCLUSIONS: Textural features had significant associations with histologic tumor types, degree of pathological differentiation, tumor proliferation and necrosis rates. Texture analysis has potential to differentiate tumor types and subtypes and to predict MLN metastasis in patients with NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Análisis de Varianza , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular , Femenino , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Mediastino/diagnóstico por imagen , Persona de Mediana Edad , Necrosis , Pronóstico , Estudios RetrospectivosRESUMEN
Este reporte corresponde al análisis de la calidad de vida de los pacientes que se incluyeron en el ensayo clínico fase III de evaluación de la vacuna CIMAvaxEGF® en cáncer de pulmón de células no pequeñas. La calidad de vida se evaluó empleando los cuestionarios EORTC QLQ-C30 y QLQ-C13, al inicio y cada 3 meses hasta el fallecimiento del paciente a criterio del investigador. Para comparar las medianas entre los dos grupos se utilizó la prueba no paramétrica de Mann-Whitney. Las comparaciones entre el nivel basal y los diferentes tiempos de seguimiento se realizaron a través de la prueba no paramétrica de Wilcoxon. El cuestionario QLQ-C30 evidenció un beneficio en cuanto a calidad de vida para el grupo vacunado con la vacuna CIMAvaxEGF® en las escalas funcionales (global, rol y social), en las escalas de síntomas de la enfermedad y del tratamiento (dolor) se observó que mejora la calidad de los mismos a favor de los pacientes tratados con la vacuna CIMAvaxEGF®. El cuestionario QLQ-C13, también evidenció ventajas para el grupo vacunado desde el punto de vista de beneficio clínico en los síntomas (disnea, disfagia, alopecia y dolor en el pecho). Se señala como significativo que disminuye la hemoptisis y la tos en el grupo vacunado, observándose un empeoramiento en el grupo control(AU)
This report corresponds to quality of life analysis of patient with non-small cell lung cancer included in the phase III clinical trials Evaluation of CIMAvaxEGF® vaccine in lung cancer. The quality of life was evaluate using the EORTC questionnaires QLQ-C30 y QLQ-C13, at the beginning and every 3 months. To compare the median between two groups the Mann-Whitney non-parametric test was used. To compare the baseline and different follows times the Wilcoxon non-parametric test was used. The QLQ-C30 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the functional scores (global, role and social) and symptoms of the disease (pain). The QLQ-LC13 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the symptoms scores (dyspnea, dysphagia, alopecia and chest pain). It is noted as significant that the hemoptysis decreases in the group vaccinated as well as the dysphagia, the cough and the dyspnea observing a worsening in the control group(AU)
Asunto(s)
Humanos , Masculino , Femenino , Calidad de Vida , Encuestas y Cuestionarios , Ensayos Clínicos Fase III como Asunto , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Vacunas contra el CáncerRESUMEN
OBJECTIVES: The aims of this study were to evaluate the relationships between textural features of the primary tumor on FDG PET images and clinical-histopathological parameters which are useful in predicting prognosis in newly diagnosed non-small cell lung cancer (NSCLC) patients. MATERIAL AND METHODS: PET/CT images of ninety (90) patients with NSCLC prior to surgery were analyzed retrospectively. All patients had resectable tumors. From the images we acquired data related to metabolism (SUVmax, metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) and texture features of primary tumors. Histopathological tumor types and subgroups, degree of Ki-67 expression and necrosis rates of the primary tumor, mediastinal lymph node (MLN) status and nodal stages were recorded. RESULTS: Among the 2histologic tumor types (adenocarcinoma and squamous cell carcinoma) significant differences were present regarding metabolic parameters, Ki-67 index with higher values and kurtosis with lower values in the latter group. Textural heterogeneity was found to be higher in poorly differentiated tumors compared to moderately differentiated tumors in patients with adenocarcinoma. While Ki-67 index had significant correlations with metabolic parameters and kurtosis, tumor necrosis rate was only significantly correlated with textural features. By univariate and multivariate analyses of the imaging and histopathological factors examined, only gradient variance was significant predictive factor for the presence of MLN metastasis. CONCLUSIONS: Textural features had significant associations with histologic tumor types, degree of pathological differentiation, tumor proliferation and necrosis rates. Texture analysis has potential to differentiate tumor types and subtypes and to predict MLN metastasis in patients with NSCLC.
RESUMEN
Se presenta el caso clínico de un anciano de 84 años de edad, fumador, con diagnóstico de cáncer de pulmón en etapa IV, quien fue incluido en el ensayo clínico de fase III para ser tratado con racotumumab. Se observó mejoría clínica y del estado general del paciente, pues según la escala funcional concluyó el estudio con ECOG 0. Por tanto, es oportuno destacar que esta vacuna incrementa la supervivencia de los afectados por cáncer de pulmón de células no pequeñas recurrentes o en estadios avanzados.
The case report of a 84 years elderly smoker, is presented with diagnosis of lung cancer in stage IV who was included in the phase III clinical trial to be treated with racotumomab. Clinical improvement and recovery of the patient's general state was observed, because according to the functional scale the study concluded with ECOG 0. Therefore, it is opportune to highlight that this vaccine increases the survival of those affected by recurrent non-small cells lung cancer or in advanced stages.
Asunto(s)
Inmunoterapia Activa , Carcinoma de Pulmón de Células no Pequeñas/terapia , Ensayo Clínico Fase III , SupervivenciaRESUMEN
OBJECTIVES: Survival heterogeneity exists among patients with non-small cell lung cancer (NSCLC), even within the same stage. We aimed to evaluate the prognostic role of pre-treatment maximum standardized uptake value (SUVmax) in patients treated with definitive concurrent chemoradiotherapy for stage III NSCLC. MATERIALS AND METHODS: Between 2010 and 2017, 103 patients with stage III NSCLC who underwent 18F-FDG PET/CT at the time of diagnosis were included in the study. RESULTS: Higher tumor stages were correlated with higher pre-treatment SUVmax of lymph nodes (LNs) (p=0.005) but were not correlated with higher SUVmax of primary tumor (p=0.2). The median SUVmax of LNs was 2.84, 8.06, and 11.11 in stage IIIa, IIIb and IIIc, respectively. Higher nodal stage was also correlated with higher SUVmax of LNs (p=0.01). According to ROC analysis, there was no significant cut-off value of SUVmax observed for primary tumor, therefore continuous variables were used for survival analyses. The best SUVmax cut-off was 3.5 for the LNs, therefore the SUVmax of LNs was evaluated as both a dichotomous and a continuous variable. Pre-treatment SUVmax of primary tumor did not predict survival outcomes but both the continuous and dichotomous variables of SUVmax of LNs predicted recurrence free survival and overall survival. Nodal stage (N0-2 vs. N3) and AJCC stage (IIIa vs IIIb vs. IIIc) were the other prognostic factors. CONCLUSIONS: Pre-treatment SUVmax of LNs had prognostic value in patients treated with definitive concurrent chemoradiotherapy for stage III NSCLC. In future trials, pre-treatment SUVmax of the LNs would serve as a guide for patients who might benefit from more aggressive treatments.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Radiofármacos/farmacocinética , Dosificación Radioterapéutica , Radioterapia Conformacional/métodos , Estudios RetrospectivosRESUMEN
Abstract: Objective: To analyze the differences in the clinico-pathological and molecular characteristics of non-small cell lung cancer (NSCLC) as well as the clinical outcome of patients by sex and hormonal status. Materials and methods: We performed a retrospective study among 1 104 NSCLC patients. Clinic-pathologic data was recorded and survival outcomes were compared between male and female sex patients, and further by pre and postmenopausal status in females. Results: Women were significantly more likely to be non-smokers (p<0.001), had higher frequency of wood-smoke exposure (p<0.001), EGFR-sensitizing mutations (p<0.001), had better performance status (p=0.020) and had a better overall survival (OS) compared to men (p=0.021). Differences were found also by hormonal status, postmenopausal women had a longer OS compared to premenopausal women (31.1 vs. 19.4 months p=0.046). Conclusion: Our results support the differences in lung cancer presentation by sex and also by hormonal status.
Resumen: Objetivo: Analizar las diferencias en las características clínico-patológicas, moleculares y en la evolución del cáncer de pulmón de células no pequeñas (CPCNP) por sexo y estadio hormonal. Material y métodos: Estudio retrospectivo (N=1 104) en pacientes con CPCNP. Se recabaron datos clínico-patológicos y desenlaces de sobrevida y se compararon entre hombres y mujeres, y entre mujeres pre y postmenopáusicas. Resultados: Las mujeres de este estudio tuvieron significativamente mayor probabilidad de ser no fumadoras (p<0.001), tener exposición a humo de leña (p<0.001), mutaciones en EGFR (p<0.001), mejor estado funcional (p=0.020), y una mejor sobrevida global (SG) en comparación con los hombres (p=0.021). Estas diferencias también se encontraron en cuestión al estatus hormonal, con las mujeres postmenopáusicas presentando una mayor sobrevida en comparación con las premenopáusicas (31.1 vs. 19.4 meses; p=0.046). Conclusión: Los presentes resultados apoyan las diferencias en la presentación del CPCNP de acuerdo con el sexo y estatus hormonal.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Factores Sexuales , Tasa de Supervivencia , Estudios Retrospectivos , Premenopausia , Posmenopausia , MéxicoRESUMEN
Se realizó un estudio descriptivo y longitudinal de 58 pacientes con cáncer de pulmón de células no pequeñas, atendidos en la consulta de Sombras Pulmonares correspondiente al Servicio de Neumología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero del 2013 hasta igual mes del 2018, quienes eran tratados con CIMAvax-EGF® como práctica médica habitual, con vistas a determinar las características clinicoepidemiológicas de estos. En la serie primaron el sexo masculino y las edades de 60 a 79 años; asimismo, resultaron más frecuentes la etapa IV de la enfermedad y el adenocarcinoma como variedad histológica. Con el uso de la vacuna la mayoría de los pacientes presentaron una supervivencia de 12,9 meses y una respuesta terapéutica de enfermedad no progresora
A descriptive and longitudinal study of 58 patients with lung cancer of non small cells, assisted in the service of Lung Shades corresponding to the Pneumology Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital was carried out in Santiago de Cuba, from January, 2013 to the same month of 2018, who were treated with CIMAvax-EGF® as habitual medical practice, with the aim of determining the clinical and epidemiological characteristics of them. The male sex and ages from 60 to 79 years prevailed in the series; also, stage IV of the disease and the adenocarcinoma as histological variety were more frequent. With the use of the vaccine most of the patients presented a survival of 12.9 months and a therapeutic response of the non progressive disease
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Vacunas contra el Cáncer/uso terapéutico , Neoplasias Pulmonares/terapia , Atención Secundaria de Salud , Epidemiología Descriptiva , Estudios LongitudinalesRESUMEN
BACKGROUND: Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. OBJECTIVE: To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. METHODS: Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. RESULTS: Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. CONCLUSIONS: Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To test a software application for the quantification of metabolic heterogeneity and to evaluate its superiority in relation to visual interpretation. To investigate if a quantitative analysis adds information to the interpretation of 18F-FDG-PET/CT. MATERIAL AND METHODS: The study analyzed 215 patients with a 18F-FDG-PET/CT done for the initial staging of lung cancer between March 2011 and December 2015. The study included 57 (26.5%) women and 158 (73.5%) men, with ages ranging from 34 to 88 years (mean±SD: 67.23±10.04). There were 82 surgical stages (I, II, IIIA), and 133 non-surgical stages (IIIB, IV). The primary tumour was analyzed quantitatively by obtaining the following parameters: SUVmax, metabolic active tumour volume (MATV), total lesion glycolysis (TLG), and the entropy heterogeneity index (ET). Heterogeneity was assessed visually. Death dates and/or the follow-up time were registered, ranging from 0.70 to 67.60 months (mean±SD: 23.20±17.68). RESULTS: In multivariate analysis, ET emerged as a better predictor of survival than visual analysis of heterogeneity that was not statistically significant. The C-index determination demonstrated that all quantitative parameters were statistically-significant predictors of survival. Cut-offs were obtained in order to compare survival times. A multivariate analysis was performed. In the total population, the best predictor was the TNM stage, but MATV, ET, and male gender were statistically significant and independent predictors of survival. In stages without surgical indication, the best predictor was the TNM stage, but the MATV and male gender were statistically significant and independent predictors of survival. In the surgical stages, ET was the only statistically significant and independent predictor of survival. CONCLUSIONS: Quantification adds prognostic information to the visual analysis of 18F-FDG-PET/CT.