Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care?

OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.

Percepção de causas e risco oncológico, história familiar e comportamentos preventivos de usuários em aconselhamento oncogenético / Perception of cancer causes and risk, family history and preventive behaviors of users in oncogenetic counseling / Percepción de causas y riesgo oncológico, historia familiar y comportamientos preventivos de pacientes en asesoramiento oncogenético

O presente estudo teve como objetivo descrever a percepção de causas e risco para neoplasias, bem como associar comportamentos adotados para prevenção de tumores e história familiar dessa patologia em indivíduos com suspeita de síndromes neoplásicas hereditárias. A amostra de conveniência foi constituída por 51 usuários atendidos em um ambulatório de aconselhamento oncogenético de um hospital-escola do interior paulista. Utilizou-se um instrumento previamente traduzido e adaptado para a cultura brasileira. Os respondentes consideraram seu risco de câncer como sendo igual ao da população em geral e a história familiar de malignidades não foi estatisticamente associada à realização de exames preventivos. Os resultados deste estudo evidenciam a necessidade de intervenção dos profissionais de saúde, em especial do enfermeiro, o qual pode desenvolver atividades de educação em saúde junto a essa clientela, como um dos componentes essenciais para o cuidado de enfermagem em oncogenética.

The aims of the present study were to describe cancer causes and risk perception, and to associate behaviors adopted for the prevention of tumors and cancer family history in individuals with suspect of hereditary cancer syndromes. A convenience sample of 51 individuals was selected from an oncogenetic counseling outpatient clinic in a university hospital in the countryside of the state of São Paulo. An instrument adapted to Brazilian culture was used. The respondents considered their own risk as being the same as the population's risk, and family history was not statistically associated with the performing of preventive exams. These findings highlight the need for intervention by health professionals, especially nurses, who may conduct health education activities for this population, which is an essential component of nursing care in oncogenetics.

El estudio objetivó describir la percepción de causas y riesgo de padecer neoplasias, así como asociar comportamientos adoptados para la prevención de tumores e historia familiar de la patología en individuos con sospecha de síndromes neoplásicos hereditarios. La muestra de conveniencia se constituyó de 51 pacientes atendidos en ambulatorio de asesoramiento oncogenético de un hospital escuela del interior paulista. Se utilizó un instrumento traducido y adaptado a la cultura brasileña. Los consultados consideraron su riesgo de cáncer como equiparable al de la población en general, la historia familiar de enfermedades malignas no fue estadísticamente asociada a la realización de estudios preventivos. Los resultados del estudio demuestran la necesidad de intervención de los profesionales de salud, en especial del enfermero, el cual puede desarrollar actividades de educación en salud conjuntamente con estos sujetos, como uno de los componentes esenciales para el cuidado de enfermería en oncogenética.

Interaçäo dos efeitos de consumo de tabaco e câncer na família no risco de câncer de pulmão / Interaction of tobacco smoking and cancer in first-degree relatives on the risk of lung cancer

Através de estudo caso-controle, examina a possível modificação do efeito induzida pelo tabagismo no risco de câncer de pulmão em indivíduos referindo câncer em parentes de primeiro grau. Conduzido na Região Metropolitana de São Paulo, o estudo comporta 334 casos e 578 controle, sendo os casos indivíduos com câncer de pulmão diagnosticados de janeiro de 1989 a junho de 1991 e os controles, indivíduos recrutados nos mesmos hospitais de origem dos casos no mesmo período. Casos e controles foram entrevistados sobre a ocorrência de câncer na família, tabagismo, tabagismo passivo, ocupação, migração e condições socioeconômicas. Os riscos foram estimados pela regressão logística não condicional. O odds ratio (OR) ajustado não mostrou excesso de risco de câncer de pulmão em indivíduos com história de câncer de pulmão em familiares ou cânceres relacionados ao tabaco em familiares. Os resultados sugerem que câncer na família pode ser importante no risco de câncer de pulmão entre pessoas que fumam intensamente. A falta de informação sobre tabagismo entre familiares limita a interpretação destes resultados

Monitoring of molecular ans cytogenetic damage in lymphocytes from three persons with polycystic kidney disease

Background. Much interest has been generated in the studies that would help to under stand whether is a causal association between disease and various types of molecular or cytogenetic damage detected in human cells. Materials and Methods. The aims of this study were to elicit the possible association between DNA and cytogenetic damage induced in lymphocytes of three members of a family with autosomal dominant polycystic kidney disease (ADPKD). Ther predictability to develop cancer or to sensitive response to enviromental exposure of the young girl at the age of 19, her brother (9 years old) and a maternal aunt at the age of 41 were sought. Cytogenetic studies, analysis of DNA damage by single cell gel electrophoresis assay (SCGE known as a Comet assay), and analysis of p21ras protein level in blood plasma were carried out on their lymphocytes. Results. The analysis for presence of chromosome aberrations in the first mitosis and sister chromatid exchanges in the second mitosis revealed elevated levels of cytogenetic biomarkers when compared to the mean values observed in the reference group in environmental biological monitoring studies. Results of sister chromatid exchanges (SCE) and percent of cells with elevated number of exchanges (high frequency cells) that were significantly higher in two probands had demonstrated susceptibility to or possibility of enviromental exposure (pesticides, smoking). The results of this study show that the lymphocytes of two persons revealed increased sensitivity to 0.5 Gy dose of gamma radiation expressed in the increased, atthough statistically insignificant, damage detected on the molecular level after cell irradiation. Conclusions. The latter might be associated with a specific aberration present in the cells of these persons. But final conclusions can be arrived at when an application of FISH technique is completed

Antecedentes familiares como factores de riesgo / Familiar antecedents as risk factors

En el presente estudio se analizó la tendencia familiar de cinco patologías: hipertensión arterial esencial (HTA), diabetes mellitus (DM), cardiopatía isquémica crónica (CIC), accidentes cerebrovasculares (ACV), y neoplasias malignas (Ca), y la posible relación entre cada una de ellas como factor de riesgo en base a los antecedentes maternos o paternos de 258 pacientes hospitalizados (datos obtenidos del 17 al 26 de enero de 1991, Hospital Vargas), Al comparar los grupos de pacientes que sufrían alguna de las cinco patologías mencionadas con el grupo de pacientes hospitalizados por patologías distintas (grupo control) se observaron asociaciones estadísticamente significativas entre: a) antecedentes maternos o paternos de A y prevalencia de ACV; b) antecendentes maternos de la de CIC y prevalencia de CIC e HTA; c) antecedentes maternos o paternos de ACV y prevalencia de ACV y Ca; y d) antecedentes maternos de Ca y prevalencia de HTA. Estas asociaciones pudieran apoyar la idea de que el antecedente familiar de una patología pudiera constituir un fator de riesgo no sólo para esa misma patología, sino también para otras tal vez genéticamente relacionadas. Nuevos estudios, con mayor muestra y diferentes variables, serían necesarios para explotar más a fondo estas supuestas asociaciones