Supervivencia de pacientes con cáncer de pulmón de células no pequeñas en estadios avanzados. Matanzas / Survival of patients with non-small cells lung cancer in advanced stages. Matanzas

RESUMEN Introducción: el cáncer de pulmón de células no pequeñas en estadios avanzados tiene una alta incidencia y mortalidad. Los tratamientos que se emplean son la quimioterapia, la radioterapia, las terapias dirigidas y la inmunoterapia. Es preferible que los tratamientos se realicen en el marco de ensayos clínicos. Tiene una precaria supervivencia a los cinco años del diagnóstico. Objetivo: determinar la supervivencia global de los pacientes con cáncer de pulmón de células no pequeñas, en estadios avanzados. Materiales y métodos: estudio descriptivo, retrospectivo en pacientes con diagnóstico cito-histológico de cáncer de pulmón de células no pequeñas, en estadios avanzados. De un universo de 463 pacientes atendidos en el Servicio de Oncología Provincial de Matanzas, se conformó una muestra de 348. Período comprendido desde enero del 2013 a diciembre del 2016. Las variables estudiadas se tomaron de las historias clínicas y la base de datos nacional de fallecidos por cáncer de pulmón. Resultados: la mayoría de los pacientes se diagnosticaron en etapa IV (71,69 %), la modalidad de tratamiento más utilizada fue la quimioterapia (61,2 %). Los fármacos más empleados fueron las sales de platino en el78,73 %. La supervivencia global en la etapa IV fue de 1,23 % a cinco años. La modalidad de tratamiento de mayor supervivencia fue la inmunoterapia, con 3,33 % y la supervivencia global fue de 2 %. Conclusiones: predominó la etapa IV de la enfermedad. La quimioterapia a base de sales de platino como esquema de tratamiento de primera línea y la inmunoterapia como modalidad de tratamiento reportaron mayor supervivencia global, aunque esta fue precaria (AU).

ABSTRACT Introduction: non-small cell lung cancer in advanced stages shows a high incidence and mortality. The treatments used against it are chemotherapy, radiotherapy, directed therapies and immunotherapy. It is better to perform the treatments in the context of clinical trials. It has a precarious survival at the fifth year after diagnosis. Objective: to determine the global survival of patients with non-small cell lung cancer in advanced stages. Materials and methods: descriptive, retrospective study in patients with cyto-histological diagnosis of non-small lung cancer in advanced stages. A sample of 348 patients was formed from the universe of 463 patients who attended the Provincial Service of Oncology in the period from January 2013 to December 2016. The studied variables were taken from the clinical records and the national database of deceased due to lung cancer. Results: most of patients were diagnosed at the stage IV (71.69 %); the most used treatment modality was chemotherapy (61.2). The most used drugs were platinum salts in 78.73 %. The global survival at the IV stage was 1.23 at five years. The treatment modality of greater survival was immunotherapy, with 3.33 % and the global survival was 2 %. Conclusions: the disease's stage IV predominated. The platinum salts-based chemotherapy as the first line treatment scheme and immunotherapy as treatment modality provided higher global survival, although it was precarious (AU).

Respuesta al tratamiento con poliquimioterapia en pacientes con carcinoma no microcítico / Treatment response to polychemotherapy in patients with non-microcytic carcinoma

Introducción: El cáncer de pulmón constituye una de las principales causas de muerte en Cuba. La mayoría de los enfermos acuden al servicio de salud en etapa avanzada de la enfermedad, la poliquimioterapia es uno de los tratamientos utilizados. Objetivos: Evaluar la respuesta al tratamiento con cisplatino-etopósido vs cisplatino-paclitaxel, en pacientes con carcinoma no microcítico en estadios avanzado de la enfermedad. Métodos: Se realizó un estudio descriptivo, prospectivo, en 40 pacientes diagnosticados con carcinoma no microcítico en estado avanzado de la enfermedad, que fueron asignados de forma aleatoria a uno de los dos grupos de tratamiento de cisplatino + etopósido (n=20) y cisplatino + paclitaxel (n=20) en el Hospital Neumológico Benéfico Jurídico en el período comprendido desde enero de 2017 a septiembre de 2018. Resultados: Predominaron pacientes del sexo masculino entre 50 a 69 años de edad, 37,5 por ciento en estadio IV. En 72,5 por ciento de los pacientes se encontró una respuesta clínica al tratamiento, en la modalidad de cisplatino + etopósido 70 por ciento y en cisplatino + paclitaxel 75 por ciento respectivamente. Se observó un porcentaje similar de respuesta objetiva antitumoral, 32,5 por ciento de los pacientes tuvieron una reducción parcial de la lesión tumoral, mientras que en otro 32,5 por ciento se observó estabilidad de la enfermedad. Por el contrario, en 35 por ciento restante hubo progresión de la enfermedad. Conclusiones: Se concluye que ambas modalidades tienen una efectividad similar en la evolución clínico-radiológica de los enfermos de carcinoma no microcítico en etapa avanzada(AU)

Introduction: Lung cancer constitutes one of the main causes of death in Cuba. Most of the patients come to the health service at an advanced stage of the disease. Polychemotherapy is one of the treatments used. Objectives: To assess the response to treatment with cisplatin-etoposide vs. cisplatin-paclitaxel, in patients with advanced non-small cell carcinoma. Methods: A descriptive, prospective study was conducted in 40 patients diagnosed with advanced non-small cell carcinoma. They were randomly assigned to one of the two treatment groups: cisplatin + etoposide (n = 20) and cisplatin. + paclitaxel (n = 20) at the Pneumologic Hospital from January 2017 to September 2018. Results: Male patients predominated, ages ranged between 50 and 69 years, 37.5 percent were in stage IV. Clinical response to treatment was found in 72.5 percent of patients, that is, 70 percent in the modality of cisplatin + etoposide and 75 percent in cisplatin + paclitaxel. Similar percentage of objective antitumor response was observed, that is, 32.5 percent of the patients had partial reduction of the tumor lesion, while disease stability was observed in 32.5 percent . In contrast, in the remaining 35.0 percent , disease progression was observed. Conclusions: Both modalities are concluded to have similar effectiveness in the clinical-radiological evolution of persons suffering from non-microcytic carcinoma in advanced stage(AU)

Robotic thoracic surgery for non-small cell lung cancer: initial experience in Brazil / Cirurgia torácica robótica no tratamento do câncer de pulmão de células não pequenas: experiência inicial no Brasil

ABSTRACT Objective: To describe the morbidity, mortality, and rate of complete resection associated with robotic surgery for the treatment of non-small cell lung cancer in Brazil, as well as to report the rates of overall survival and disease-free survival in patients so treated. Methods: This was a retrospective study of patients diagnosed with non-small cell lung carcinoma and undergoing resection by robotic surgery at one of six hospitals in Brazil between February of 2015 and July of 2018. Data were collected retrospectively from the electronic medical records. Results: A total of 154 patients were included. The mean age was 65 ± 9.5 years (range, 30-85 years). The main histological diagnosis was adenocarcinoma, which was identified in 128 patients (81.5%), followed by epidermoid carcinoma, identified in 14 (9.0%). Lobectomy was performed in 133 patients (86.3%), and segmentectomy was performed in 21 (13.7%). The mean operative time was 209 ± 80 min. Postoperative complications occurred in 32 patients (20.4%). The main complication was air leak, which occurred in 15 patients (9.5%). The median (interquartile range) values for hospital stay and drainage time were 4 days (3-6 days) and 2 days (2-4 days), respectively. There was one death in the immediate postoperative period (30-day mortality rate, 0.5%). The mean follow-up period was 326 ± 274 days (range, 3-1,110 days). Complete resection was achieved in 97.4% of the cases. Overall mortality was 1.5% (3 deaths), and overall survival was 97.5%. Conclusions: Robotic pulmonary resection proved to be a safe treatment for lung cancer. Longer follow-up periods are required in order to assess long-term survival.

RESUMO Objetivo: Descrever morbidade, mortalidade e completude da ressecção associadas à cirurgia robótica para o tratamento de câncer de pulmão não pequenas células no Brasil, assim como sobrevida global e sobrevida livre de doença. Métodos: Estudo retrospectivo incluindo pacientes com diagnóstico de carcinoma pulmonar de células não pequenas submetidos à ressecção anatômica por cirurgia robótica em seis hospitais brasileiros entre fevereiro de 2015 e julho de 2018. Os dados foram coletados retrospectivamente de prontuários eletrônicos. Resultados: Foram incluídos 154 pacientes. A média de idade foi de 65,0 ± 9,5 anos (variação: 30-85 anos). Adenocarcinoma foi o principal tipo histológico, em 128 pacientes (81,5%), seguido por carcinoma epidermoide, em 14 (9,0%). Lobectomia foi o tipo de cirurgia mais frequente, em 133 pacientes (86,3%), seguida por segmentectomia anatômica, em 21 (13,7%). A média de tempo operatório foi de 209 + 80 min. Complicações pós-operatórias ocorreram em 32 pacientes (20,4%). Fístula aérea foi a principal complicação, em 15 pacientes (9,5%). A mediana (intervalo interquartil) de permanência hospitalar foi de 4 dias (3-6 dias) e a de tempo de drenagem foi de 2 dias (2-4 dias). Houve mortalidade operatória em 1 paciente (0,5%). O tempo médio de seguimento foi de 326 + 274 dias (variação: 3-1.110 dias). A ressecção foi completa em 97,4% dos casos. A mortalidade geral foi de 1,5% (n = 3), com sobrevida global de 97,5%. Conclusões: A ressecção pulmonar anatômica robótica no tratamento do câncer de pulmão demonstrou ser segura. Um maior tempo de seguimento é necessário para avaliar a sobrevida de longo prazo.

Pretreatment plasma fibrinogen level as a prognostic biomarker for patients with lung cancer

Many researchers have shown that pretreatment plasma fibrinogen levels are closely correlated with the prognosis of patients with lung cancer (LC). In this study, we thus performed a meta-analysis to systematically assess the prognostic value of pretreatment plasma fibrinogen levels in LC patients. A computerized systematic search in PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) was performed up to March 15, 2018. Studies with available data on the prognostic value of plasma fibrinogen in LC patients were eligible for inclusion. The pooled hazard ratios (HRs) and odd ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the correlation between pretreatment plasma fibrinogen levels and prognosis as well as clinicopathological characteristics. A total of 17 studies with 6,460 LC patients were included in this meta-analysis. A higher pretreatment plasma fibrinogen level was significantly associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.39-1.77; p=0.001), disease-free survival (DFS) (HR: 1.53; 95% CI: 1.33-1.76; p=0.003), and progression-free survival (PFS) (HR: 3.14; 95% CI: 2.15-4.59; p<0.001). Furthermore, our subgroup and sensitivity analyses demonstrated that the pooled HR for OS was robust and reliable. In addition, we also found that a higher fibrinogen level predicted advanced TNM stage (III-IV) (OR=2.18, 95% CI: 1.79-2.66; p<0.001) and a higher incidence of lymph node metastasis (OR=1.74, 95% CI: 1.44-2.10; p=0.02). Our study suggested that higher pretreatment plasma fibrinogen levels predict worse prognoses in LC patients.

La inmunoterapia una alternativa terapéutica en ancianos con cáncer de pulmón de células no pequeñas / Immunotherapy, a therapeutic option in elder people with non small cells lung cancer

RESUMEN El cáncer es un problema prioritario de salud pública en el mundo. En Cuba constituye la segunda causa de muerte en la mayoría de grupos de edades y fundamentalmente en la población mayor de 60 años. El objetivo fue evaluar el impacto de la inmunoterapia como una alternativa terapéutica que mejora las funciones de supervivencia en pacientes ancianos con cáncer de pulmón de células no pequeñas. Se realizó un estudio analítico experimental donde el universo estuvo integrado por 123 ancianos con diagnóstico de cáncer de pulmón los cuales fueron tratados con inmunoterapia en Matanzas. Fueron utilizadas variables de control a las cuales se les aplicaron las medidas de resumen correspondientes utilizando las pruebas de hipótesis de chi cuadrado y las razones de verosimilitud para su análisis y estadístico y fueron evaluadas las funciones de supervivencia usando las curvas de Kaplan Meier. Se demostró la eficacia y seguridad de la inmunoterapia en el tratamiento de los pacientes estudiados. Por ello consideramos que el impacto secuencial de la combinación de la cirugía, la quimioterapia, la radioterapia y las terapias biológicas, tiende a prolongar la supervivencia de los pacientes que sufren cáncer de pulmón de células no pequeñas con una calidad de vida éticamente aceptable. Las nuevas terapias inmunológicas que consisten en devolver al sistema inmunológico de los pacientes, la capacidad de reconocer al tumor como extraño, y por tanto luchar contra él; han producido respuestas y beneficios muy importantes (AU).

SUMMARY Cancer is a priority public health problem in the world. In Cuba, it is the second cause of death in most age groups and mainly in the population aged over 60 years. To evaluate the impact of immunotherapy as a therapeutic alternative that improves survival functions in elder patients with non-small cell lung cancer. An experimental analytical study was carried out; the universe was composed by 123 elder people diagnosed with lung cancer who were treated with immunotherapy in Matanzas. Control variables were used to which the corresponding summary measures were applied using chi-square hypothesis tests and likelihood ratios for their analysis and statistics; survival functions were evaluated using Kaplan Meier curves. The efficacy and safety of immunotherapy in the treatment of the studied patients was demonstrated. Therefore, the authors believe that the sequential impact of the combination of surgery, chemotherapy, radiotherapy and biological therapies tends to extend the survival of patients suffering from non-small cell lung cancer with an ethically acceptable life quality. The new immunological therapy, consisting in returning to the patients´ immunologic system the capacity of recognizing a tumor as foreign, and therefore, fighting against it, have yielded very important answers and benefits (AU).

Characteristics of non-small cell lung cancer: differences by sex and hormonal status in a Mexican population / Características del cáncer de pulmón de células no pequeñas: diferencias por sexo y estado hormonal en una población mexicana

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.

Proportional weight loss in six months as a risk factor for mortality in stage IV non-small cell lung cancer / Perda de peso proporcional em seis meses como fator de risco para mortalidade no câncer de pulmão de células não pequenas estádio IV

ABSTRACT Objective: To evaluate different weight loss (WL) cut-off points as prognostic markers of 3-month survival after diagnosis of stage IV non-small cell lung cancer (NSCLC). Methods: This was a prospective study involving 104 patients with metastatic (stage IV) NSCLC who were admitted to a cancer treatment center in southern Brazil between January of 2014 and November of 2016. We evaluated total WL and WL per month, as well as WL and WL per month in the 6 months preceding the diagnosis. The patients were followed for 3 months after diagnosis. A Cox proportional hazards regression model and Kaplan-Meier curves were used in order to evaluate 3-month survival. Results: The median WL in the 6 months preceding the diagnosis was 6% (interquartile range, 0.0-12.9%). Patients with WL ≥ 5% had a median survival of 78 days, compared with 85 days for those with WL < 5% (p = 0.047). Survival at 3 months was 72% for the patients with WL ≥ 5% (p = 0.047), 61% for those with WL ≥ 10% (p < 0.001), and 45% for those with WL ≥ 15% (p < 0.001). In the multivariate analysis, the hazard ratio for risk of death was 4.51 (95% CI: 1.32-15.39) for the patients with WL ≥ 5%, 6.34 (95% CI: 2.31-17.40) for those with WL ≥ 10%, and 14.17 (95% CI: 5.06-39.65) for those with WL ≥ 15%. Conclusions: WL in the 6 months preceding the diagnosis of NSCLC is a relevant prognostic factor and appears to be directly proportional to the rate of survival at 3 months.

RESUMO Objetivo: Avaliar diferentes pontos de corte da perda de peso (PP) como marcadores prognósticos de sobrevida em 3 meses após o diagnóstico de câncer de pulmão de células não pequenas estádio IV (CPCNP). Métodos: Estudo prospectivo envolvendo 104 pacientes com CPCNP metastático (estádio IV) que foram internados em um centro de tratamento de câncer no sul do Brasil entre janeiro de 2014 e novembro de 2016. Avaliamos a PP total e PP por mês, bem como PP e PP por mês nos 6 meses anteriores ao diagnóstico. Os pacientes foram acompanhados por 3 meses após o diagnóstico. Um modelo de regressão de riscos proporcionais de Cox e curvas de Kaplan-Meier foram utilizados para avaliar a sobrevida em 3 meses. Resultados: A mediana da PP nos 6 meses anteriores ao diagnóstico foi de 6% (intervalo interquartil, 0,0-12,9%). Pacientes com PP ≥ 5% tiveram uma sobrevida mediana de 78 dias, comparados a 85 dias para aqueles com PP < 5% (p = 0,047). A sobrevida em 3 meses foi de 72% para os pacientes com PP ≥ 5% (p = 0,047), 61% para aqueles com PP ≥ 10% (p < 0,001) e 45% para aqueles com PP ≥ 15% (p < 0,001). Na análise multivariada, a taxa de risco para óbito foi de 4,51 (IC95%: 1,32-15,39) para os pacientes com PP ≥ 5%, 6,34 (IC95%: 2,31-17,40) para aqueles com PP ≥ 10%, e 14,17 (IC95%: 5,06-39,65) para aqueles com PP ≥ 15%. Conclusões: A PP nos 6 meses anteriores ao diagnóstico de CPCNP é um fator prognóstico relevante e parece ser diretamente proporcional à taxa de sobrevida em 3 meses.

Survival in a cohort of patients with lung cancer: the role of age and gender in prognosis / Sobrevida em uma coorte de pacientes com câncer de pulmão: papel da idade e do sexo no prognóstico

ABSTRACT Objective: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. Methods: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. Results: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. Conclusions: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.

RESUMO Objetivo: Analisar características demográficas e clínicas, assim como a evolução de pacientes com câncer de pulmão de células não pequenas (CPCNP) de acordo com a faixa etária e o sexo desses pacientes. Métodos: Coorte retrospectiva de pacientes diagnosticados com CPCNP entre janeiro de 2000 e julho de 2012, acompanhados até julho de 2015, em um hospital terciário de referência no município de São Paulo. Com base na distribuição de idade segundo os percentis 25 e 75, os pacientes foram estratificados em três grupos: < 55 anos; ≥ 55 e < 72 anos; e ≥ 72 anos. O tempo de sobrevida foi avaliado durante o período de acompanhamento do estudo. As funções de sobrevida geral e por sexo estratificada por faixa etária (considerando-se óbito por qualquer motivo) foram calculadas empregando-se o método de Kaplan-Meier. As diferenças entre as curvas de sobrevida foram verificadas pelo teste log-rank. Resultados: Foram incluídos 790 pacientes, com a seguinte distribuição etária: 165, 423 e 202 pacientes, respectivamente, com < 55 anos; ≥ 55 e < 72 anos; e ≥ 72 anos. Na amostra geral, havia 493 homens (62,4%). O padrão histológico mais frequente foi adenocarcinoma nos grupos com < 72 anos; 575 pacientes (73%) apresentavam doença avançada (estádios IIIB-IV). A mediana de sobrevida em 5 anos foi de 12 meses (IC95%: 4-46), sem diferenças significantes nas faixas etárias estudadas. Conclusões: O CPCNP continua sendo mais frequente em homens, apesar de ter havido um aumento de sua proporção em mulheres na faixa etária < 55 anos. O adenocarcinoma predominou nas mulheres. Nos homens, o carcinoma escamoso predominou no grupo ≥ 72 anos. A maioria dos casos apresentava-se em estádio avançado ao diagnóstico. Não foram observadas diferenças estatísticas na sobrevida entre os sexos ou as faixas etárias.

Estimated costs of advanced lung cancer care in a public reference hospital / Estimativa dos custos da assistência do câncer de pulmão avançado em hospital público de referência

ABSTRACT OBJECTIVE To estimate the direct medical costs of advanced non-small cell lung cancer care. METHODS We assessed a cohort of 277 patients treated in the Brazilian National Cancer Institute in 2011. The costs were estimated from the perspective of the hospital as a service provider of reference for the Brazilian Unified Health System. The materials and procedures used were identified and quantified, per patient, and we assigned to them monetary values, consolidated in phases of the assistance defined. The analyses had a descriptive character with costs in Real (R$). RESULTS Overall, the cohort represented a cost of R$2,473,559.91, being 71.5% related to outpatient care and 28.5% to hospitalizations. In the outpatient care, costs with radiotherapy (34%) and chemotherapy (22%) predominated. The results pointed to lower costs in the initial phase of treatment (7.2%) and very high costs in the maintenance phase (61.6%). Finally, we identified statistically significant differences of average cost by age groups, education levels, physical performance, and histological type. CONCLUSIONS This study provides a current, useful, and relevant picture of the costs of patients with non-small cell lung cancer treated in a public hospital of reference and it provides information on the magnitude of the problem of cancer in the context of public health. The results confirm the importance of radiation treatment and hospitalizations as the main components of the cost of treatment. Despite some losses of follow-up, we assess that, for approximately 80% of the patients included in the study, the estimates presented herein are satisfactory for the care of the disease, from the perspective of a service provider of reference of the Brazilian Unified Health System, as it provides elements for the management of the service, as well as for studies that result in more rational forms of resource allocation.

RESUMO OBJETIVO Estimar os custos médicos diretos da assistência ao câncer de pulmão não pequenas células avançado. MÉTODOS Foi avaliada uma coorte de 277 pacientes matriculados no Instituto Nacional do Câncer em 2011. Os custos foram estimados sob a perspectiva do hospital como prestador de serviços de referência para o SUS. Insumos e procedimentos utilizados foram identificados e quantificados, por paciente, sendo a eles atribuídos valores monetários, consolidados por fases da assistência definidas. As análises tiveram caráter descritivo com custos em reais (R$). RESULTADOS Em termos globais, a coorte representou um custo de R$2.473.559,91, sendo 71,5% relacionados à atenção ambulatorial e 28,5% as internações. Na atenção ambulatorial, predominaram os custos com radioterapia (34%) e quimioterapia (22%). Os resultados apontaram para custos menores na fase inicial de tratamento (7,2%) e custos muito elevados na fase de manutenção (61,6%). Por fim, identificaram-se diferenças estatisticamente significativas das médias dos custos por faixas etárias, níveis de escolaridade, desempenho físico e tipo histológico. CONCLUSÕES Este estudo fornece um retrato atual, útil e relevante sobre os custos de pacientes com câncer de pulmão não pequenas células assistidos em um hospital público de referência e provê elementos sobre a magnitude do problema do câncer no âmbito da saúde pública. Os resultados ratificam a importância do tratamento radioterápico e das internações como principais componentes de custo do tratamento. Apesar de algumas perdas de seguimento avalia-se que, para cerca de 80% dos pacientes incluídos no estudo, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS, fornecendo elementos para a gestão do serviço, bem como para estudos que redundem em formas mais racionais de alocação de recursos.

Chemotherapy for advanced non-small cell lung cancer in the elderly population

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making

Factors associated with disease-specific survival of patients with non-small cell lung cancer / Fatores associados à sobrevida doença-específica em pacientes com câncer de pulmão de células não pequenas

ABSTRACT Objective: Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. Methods: This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. Results: The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. Conclusions: In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer.

RESUMO Objetivo: O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na cidade do Rio de Janeiro. Métodos: Estudo retrospectivo de coorte hospitalar com 1.194 pacientes. As probabilidades de sobrevida doença-específica em 60 meses foram calculadas com o método de Kaplan-Meier para três grupos de estadiamento. A importância dos fatores estudados foi avaliada por um modelo teórico hierarquizado após o ajuste de modelos de regressão múltipla de Cox. Resultados: Foi estimada uma taxa de letalidade doença-específica em 60 meses de 86,0%. A probabilidade de sobrevida doença-específica em 60 meses variou de 25,0%, nos estádios iniciais, a 2,5%, no estádio IV. A situação funcional, a intenção e a modalidade do tratamento inicial foram os principais fatores prognósticos identificados na população estudada. Conclusões: As probabilidades de sobrevida doença-específica estimadas na amostra estudada foram muito baixas, e não foram identificados fatores que pudessem ser modificados após o diagnóstico visando uma melhora da sobrevida. A prevenção primária, como a redução da prevalência do tabagismo, ainda é a melhor forma de evitar que mais pessoas sofram as consequências do câncer de pulmão.

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; Pheterogeneity=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; Pheterogeneity=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; Pheterogeneity=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; Pheterogeneity=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer. .

The impact of erlotinib use in non-small-cell lung cancer patients treated in a private reference general hospital and in a private cancer clinic from 2005 to 2011 / O impacto do uso do erlotinibe em pacientes portadores de neoplasia de pulmão de não pequenas células tratados em um hospital geral de referência e clínica particular de oncologia no período de 2005 a 2011

ABSTRACT Objective: To report the demographic data and clinical outcomes of non-small-cell lung cancer patients exposed to erlotinib in any line of treatment. Methods: This was a retrospective cohort study of nonsmall-cell lung cancer patients from a reference general hospital and a private oncology clinic, who received erlotinib from 2005 to 2011. Statistical analysis was performed and we evaluated demographic data and response to treatment, by correlating the results of this first cohort published in Brazil with results of current literature. Results: A total of 44 patients were included; 65.9% were diagnosed with adenocarcinoma, and 63.6% had metastatic disease. The mean age was 63.3 years. The median follow-up was 47.9 months. Epidermal growth factor receptor mutation screening was performed in 22.7% of patients (n=10), with mutation present in 30% of patients. The median overall survival was 46.3 months, and there was a higher probability of survival at 60 months for females compared to males (29.4% versus 15.8%; p=0.042). The other variables did not present significant statistical difference. Conclusion: We collected the largest cohort of patients with non-small-cell lung cancer who have used erlotinib in Brazil to date, and demonstrated that outcomes of patients treated at our clinic during the study period were consistent with the results of current literature in similar patients. .

RESUMO Objetivo: Relatar as características demográficas e a evolução de pacientes com neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento. Métodos: Coletamos retrospectivamente dados de pacientes portadores de neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento em um hospital geral de referência e em uma clínica particular de oncologia em São Paulo, no período de 2005 a 2011. Foi realizada a análise estatística e foram avaliados aspectos demográficos e resposta ao tratamento estabelecido, correlacionando os resultados dessa primeira coorte publicada no Brasil com resultados da literatura vigente. Resultados: Foram avaliados 44 pacientes, dos quais 65,9% eram portadores de adenocarcinoma e 63,6% tinham doença metastática. A média de idade foi de 63,3 anos. O seguimento mediano foi de 47,9 meses. A pesquisa de mutação do receptor do fator de crescimento epidérmico foi realizada em 22,7% dos pacientes (n=10), resultando positiva em 30% dos avaliados. A sobrevida global mediana foi de 46,3 meses, e observou-se uma probabilidade maior de sobrevida em 60 meses para o grupo feminino, quando comparado ao grupo masculino (29,4% versus 15,8%; p=0,042). As demais variáveis não apresentaram diferença estatística significativa. Conclusão: Coletamos a maior sequência de pacientes com neoplasia de pulmão de não pequenas células que fizeram uso de erlotinibe no Brasil até a data vigente e demonstramos que a evolução dos pacientes tratados no período avaliado teve resultados concordantes com os da literatura vigente em pacientes semelhantes. .

Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a SEER analysis

Purposes To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. Materials and Methods From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. Results Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. Conclusion The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era. .

Efficacy of Surgical Treatment for Brain Metastasis in Patients with Non-Small Cell Lung Cancer

PURPOSE: Patients with non-small cell lung cancer (NSCLC) and simultaneously having brain metastases at the initial diagnosis, presenting symptoms related brain metastasis, survived shorter duration and showed poor quality of life. We analyzed our experiences on surgical treatment of brain metastasis in patients with NSCLC. MATERIALS AND METHODS: We performed a single-center, retrospective review of 36 patients with NSCLC and synchronous brain metastases between April 2006 and December 2011. Patients were categorized according to the presence of neurological symptoms and having a brain surgery. As a result, 14 patients did not show neurological symptoms and 22 patients presented neurological symptoms. Symptomatic 22 patients were divided into two groups according to undergoing brain surgery (neurosurgery group; n=11, non-neurosurgery group; n=11). We analyzed overall surgery (OS), intracranial progression-free survival (PFS), and quality of life. RESULTS: Survival analysis showed there was no difference between patients with neurosurgery (OS, 12.1 months) and non-neurosurgery (OS, 10.2 months; p=0.550). Likewise for intracranial PFS, there was no significant difference between patients with neurosurgery (PFS, 6.3 months) and non-neurosurgery (PFS, 5.3 months; p=0.666). Reliable neurological one month follow up by the Medical Research Council neurological function evaluation scale were performed in symptomatic 22 patients. The scale improved in eight (73%) patients in the neurosurgery group, but only in three (27%) patients in the non-neurosurgery group (p=0.0495). CONCLUSION: Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms.

Clinical experience on use of oral EGFR-TKIs as first-line treatment of advanced NSCLC from a tertiary care centre in North India and implications of skin rash.

Background. Limited data are available from India on treatment outcomes with oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in newly diagnosed non-small cell lung cancer (NSCLC). We studied the demographic profile and treatment outcomes of patients with NSCLC, receiving first-line treatment with oral EGFR-TKIs. Methods. Retrospective study of newly diagnosed NSCLC patients treated with oral EGFR-TKIs over a 4-year period at a tertiary care institute in North India. Results. Of 76 patients studied, females and non-smokers constituted 32.9% and 48.7%, respectively. Majority of patients had adenocarcinoma (59.2%), stage IV (64.5%) disease and Karnofsky performance status <70 (74.5%). Gefitinib was the most frequently used EGFR-TKI (92.1%). Most common indication for the use of EGFR-TKIs was poor performance status (65.8%). Among assessable patients, disease control and progressive disease were evident in 66% and 34%, respectively. Most common side effects were skin rash (17%) and diarrhoea (10.6%). Patients with and without skin rash differed significantly in relation to objective response to treatment (100% versus 23.1%) and overall survival (median not reached versus 178 days). On multivariate logistic regression analysis, malignant pleural effusion was associated with occurrence of rash (odds ratio=0.19; 95% confidence interval = 0.04-0.95; p=0.04). Conclusions. Oral EGFR-TKIs appear to be useful for the treatment of clinically selected patients with advanced NSCLC. Occurrence of skin rash was independently associated with treatment response and better survival in the current study.

Role of gender in the survival of surgical patients with nonsmall cell lung cancer

There are reports of greater survival rates in nonsmall cell lung cancer [NSCLC] patients of female gender. The objective of this study was to evaluate the role of gender in survival of NSCLC patients treated surgically with curative intent [stage I/II]. In a retrospective cohort design, we screened 498 NSCLC patients submitted to thoracotomies at the hospital Sao Lucas, in Porto Alegre, Brazil from 1990 to 2009. After exclusion of patients that did not fit to all the inclusion criteria, we analyzed survival rates of 385 subjects. Survival was analyzed using the Kaplan-Meier method. The Cox regression model was used to evaluate potential confounding factors. Survival rates at 5 and 10 years were 65.3% and 49.5% for women and 46.5% and 33.2% for men, respectively [P = 0.006]. Considering only stage I patients, the survival rates at 5 and 10 years were 76.2% and 55.1% for women and 50.7% and 35.4% for men, respectively [P = 0.011]. No significant differences in survival rates were found among stage II patients. Our results show female gender as a possible protective factor for better survival of stage I NSCLC patients, but not among stage II patients. This study adds data to the knowledge that combined both genders survival rates for NSCLC is not an adequate prognosis

XPG is a novel biomarker of clinical outcome in advanced non-small-cell lung cancer

Polymorphisms in XPG were considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We investigated the impact of several potential SNPs of XPG on the efficacy of platinum-based chemotherapy in NSCLC patients. A total of 433 patients were consecutively selected between Nov. 2006 and Dec. 2007, and were followed-up up to Nov. 2011. The genotyping of six SNPs [rs2296147, rs751402, rs873601, rs4150375, rs17655 and rs2094258] were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. Patients carrying CT+TT genotype of rs2296147 had a significantly longer median PFS [17.5 months] and OS [26.8 months] than CC genotype. Hazard ratio [HR] for PFS and OS in patients with CT+TT genotype of rs2296147 was respectively 0.73[0.51-0.97] and 0.66[0.48-0.99] when compare CC genotype, respectively. Similarly, patients with rs2094258 AG+GG genotype had a longer median progression time [18.4 months] and overall survival time [27.3 months] when compared with those with AA genotype, and HRs[95% CI] for PFS and OS were 0.44[0.34-0.78] and 0.51[0.39-0.82], respectively. Our study suggests rs2296147 CT+TT and rs2094258 AG+GG genotypes contribute to the better survival of NSCLC. Our study provides significant information on role of prognostic value of XPG SNPs, and detecting of XPG could be used as predictive markers toward individualizing NSCLC treatment strategies