RESUMO
OBJECTIVE: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes. MATERIALS AND METHODS: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development. RESULTS: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them. CONCLUSIONS: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients.
OBJETIVO: El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. MATERIAL Y MÉTODOS: Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tec- nológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Ins- tituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. RESULTADOS: Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. C. CONCLUSIONES: Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervenção Médica Precoce , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de NeoplasiasRESUMO
Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as 68Ga-DOTA-E-[c(RGDfK)]2, that target αvß3 integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. Methods: From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All patients underwent PET/CT with 68Ga-DOTA-E-[c(RGDfK)]2 radiotracer and blood-sample tests to quantify angiogenesis factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor AB) before and after completing 2 therapy cycles. Results: Of the 38 patients, 31 had available baseline and follow-up PET/CT. Baseline lung tumor volume addressed with 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT correlated with serum vascular endothelial growth factor levels, whereas baseline lung/liver SUVmax index correlated with platelet-derived growth factor AB. After treatment, the overall response rate and disease control rate were 7.9% and 47.3%, respectively. A greater decrease in lung tumor volume (-37.2% vs. -27.6%) was associated with a better disease control rate in patients (P = 0.005). Median progression-free survival was 3.7 mo. Nonsmokers and patients with a higher baseline lung tumor volume were more likely to have a higher progression-free survival (6.4 vs. 3.74 [P = 0.023] and 6.4 vs. 2.1 [P = 0.003], respectively). Overall survival was not reached. Patients with a greater decrease in lung SUVmax (not reached vs. 7.1 mo; P = 0.016) and a greater decrease in the lung/spleen SUVmax index (not reached vs. 7.1; P = 0.043) were more likely to have a longer overall survival. Conclusion:68Ga-DOTA-E-[c(RGDfK)]2 PET/CT is a potentially useful tool for assessing responses to angiogenesis inhibitors. Further analysis and novel studies are warranted to identify patients who might benefit from this therapy.
Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Docetaxel/uso terapêutico , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel/química , Indóis/uso terapêutico , Oligopeptídeos/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenocarcinoma de Pulmão/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
The management of lung cancer is challenging. However, nowadays the main goal is to achieve a significant overall survival accompanied by a good quality of life. Because smoking is associated with up to 71% of cancer deaths, the first policy that should be established is one that promotes strategies for healthy lifestyles by providing information about lung cancer, risk factors, protection factors, and precautionary data. Furthermore, an effective screening method that would allow early diagnosis should be established. Following diagnosis, the patient should be genotyped to identify predisposing mutations to give personalized medicine to the patient. The health system policies should include information that affects the health of the population and simultaneously allows for early diagnoses, resulting in a higher survival rate.
Assuntos
Neoplasias Pulmonares/prevenção & controle , Programas Nacionais de Saúde/organização & administração , Serviços Preventivos de Saúde/organização & administração , Adolescente , Adulto , Idoso , Criança , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Genótipo , Política de Saúde , Promoção da Saúde , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Medicina de Precisão , Prevenção Primária/organização & administração , Prevenção Secundária/organização & administração , Fumar/efeitos adversos , Prevenção do Hábito de Fumar , Adulto JovemRESUMO
BACKGROUND: Up-to-date oncological therapy has been accomplished through the results of clinical trials (CTs). We analyzed the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and its relation to CT enrollment. METHODS: The study included 1,042 patients with advanced NSCLC treated at the Instituto Nacional de Cancerología. All patients received treatment according to the national and international guidelines. Data were collected from medical records. Patients were subgrouped on the basis of their CT enrollment as follows: participants in any CT (ACT), exclusively intervention CTs (ICT) or exclusively pharmaceutical-sponsored CTs (PCT). RESULTS: The CT enrollment effect was assessed through a multivariate Cox proportional hazards model. Thirty percent of the patients were in ACT, 28.3% in ICT and 13.7% in PCT. Female gender (p = 0.001), adenocarcinoma histology (p = 0.018), positive EGFR mutation (p = 0.006), and better ECOG performance status (<2) (p ≤ 0.0001) were more frequent in patients enrolled in CT; further, tobacco smoking (p ≤ 0.0001) and KRAS mutation (p = 0.001) were more frequent in patients who were not enrolled in a CT. CONCLUSION: Enrollment in ACT was associated with a better OS (hazard ratio: 0.47-0.74). NSCLC patients enrolled in a CT have an improved survival in an independent manner to other prognostic factors.
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Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos como Assunto , Neoplasias Pulmonares/mortalidade , Participação do Paciente , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores Sexuais , Fumar , Taxa de SobrevidaRESUMO
BACKGROUND: Tobacco-smoke is the major etiological factor related to lung cancer. However, other important factor is chronic wood smoke exposure (WSE). Approximately 30 % of lung cancer patients in Mexico have a history of WSE, and present different clinical, pathological and molecular characteristics compared to tobacco related lung cancer, including differences in mutational profiles. There are several molecular alterations identified in WSE associated lung cancer, however most studies have focused on the analysis of changes in several pathogenesis related proteins. METHODS: Our group evaluated gene expression profiles of primary lung adenocarcinoma, from patients with history of WSE or tobacco exposure. Differential expression between these two groups were studied through gene expression microarrays. RESULTS: Results of the gene expression profiling revealed 57 statistically significant genes (p < 0.01). The associated biological functional pathways included: lipid metabolism, biochemistry of small molecules, molecular transport, cell morphology, function and maintenance. A highlight of our analysis is that three of the main functional networks represent 37 differentially expressed genes out of the 57 found. These hubs are related with ubiquitin C, GABA(A) receptor-associated like protein; and the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: Our results reflect the intrinsic biology that sustains the development of adenocarcinoma related to WSE and show that there is a different gene expression profile of WSE associated lung adenocarcinoma compared to tobacco exposure, suggesting that they arise through different carcinogenic mechanisms, which may explain the clinical and mutation profile divergences between both lung adenocarcinomas.
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Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Fuligem/intoxicação , Poluição por Fumaça de Tabaco/efeitos adversos , Madeira/efeitos adversos , Adenocarcinoma/etiologia , Exposição Ambiental , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/etiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , TranscriptomaRESUMO
BACKGROUND: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib. METHODS: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437. RESULTS: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients. CONCLUSIONS: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients.
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Adenocarcinoma/tratamento farmacológico , Fator de Crescimento de Hepatócito/sangue , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Adenocarcinoma de Pulmão , Afatinib , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Quinazolinas/administração & dosagem , Quinazolinas/farmacologia , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/farmacologia , Resultado do TratamentoRESUMO
Abstract The management of lung cancer is challenging. However, nowadays the main goal is to achieve a significant overall survival accompanied by a good quality of life. Because smoking is associated with up to 71% of cancer deaths, the first policy that should be established is one that promotes strategies for healthy lifestyles by providing information about lung cancer, risk factors, protection factors, and precautionary data. Furthermore, an effective screening method that would allow early diagnosis should be established. Following diagnosis, the patient should be genotyped to identify predisposing mutations to give personalized medicine to the patient. The health system policies should include information that affects the health of the population and simultaneously allows for early diagnoses, resulting in a higher survival rate.
Resumen El manejo del cáncer de pulmón es un reto que tiene como objetivo una supervivencia global significativa que se vea rodeada de una buena calidad de vida. Si se considera que el tabaquismo está asociado hasta con 71% de las muertes por cáncer, la primera política que debe establecerse es la de proporcionar información sobre el cáncer de pulmón, factores de riesgo, factores de protección y datos de alarma mediante una estrategia de salud de línea de vida, además del establecimiento de un método de tamizaje efectivo que permita un diagnóstico temprano. Después del diagnóstico, debe realizarse una genotipificación para identificar mutaciones sensibles y para proporcionar un tratamiento personalizado al paciente. Las políticas del sistema de salud deben incluir información para que la población incida en su salud y también se puedan realizar diagnósticos tempranos que permitan una mayor supervivencia.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Serviços Preventivos de Saúde/organização & administração , Neoplasias Pulmonares/prevenção & controle , Programas Nacionais de Saúde/organização & administração , Prevenção Primária/organização & administração , Fumar/efeitos adversos , Predisposição Genética para Doença , Detecção Precoce de Câncer , Prevenção Secundária/organização & administração , Medicina de Precisão , Prevenção do Hábito de Fumar , Genótipo , Política de Saúde , Promoção da Saúde , Neoplasias Pulmonares/epidemiologia , México/epidemiologiaRESUMO
OBJECTIVE: Sixteen percent of US population is Hispanic, mostly Mexican. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) with non-small-cell lung cancer (NSCLC), even when most Hispanic patients are diagnosed at advanced disease stages and have lower income status. We analyzed the clinical, pathological, and molecular characteristics as well as outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox". MATERIAL AND METHODS: A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007 to 2014 was analyzed. Their clinical-pathological characteristics, the presence of EGFR and KRAS mutations and the prognosis were evaluated. RESULTS: Patients presented with disease stages II, IIIa, IIIb and IV at rates of 0.6, 4.8, 18.4 and 76.3%, respectively. NSCLC was associated with smoking in only 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 27.0% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.5% (10.3% men vs. 10.1% in women p=0.939). The median OS for all patients was 23.0 [95% CI 19.4-26.2], whereas for patients at stage IV, it was 18.5 months [95% CI 15.2-21.8]. The independent factors associated with the OS were the ECOG, disease stage, EGFR and KRAS mutation status. CONCLUSION: The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptores ErbB/genética , Feminino , Hispânico ou Latino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Fumaça/efeitos adversos , Fumar/efeitos adversos , Adulto Jovem , Proteínas ras/genéticaRESUMO
PURPOSE: Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel-platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in NSCLC patients with prior PP treatment. METHODS: Patients with stage IV NSCLC treated with PP that presented disease progression and received docetaxel as second-line treatment were included. Demographics, clinical characteristics, EGFR mutation status, objective response (OR), overall survival (OS), progression-free survival (PFS), and PFS without chemotherapy after first line with PP were analyzed. RESULTS: Sixty-three patients were evaluated. Median age was 58 years, 54% of patients were women, 53% were never-smokers, and 39% had EGFR mutations. OR and median PFS for PP were 36.5% and 6.7 months, respectively. OR and median PFS for docetaxel were 19% and 3.8 months, respectively. Patients with EGFR mutations had better response to docetaxel compared with wild-type patients (26 vs. 17%, p = 0.028). However, only long PFS (>6 months) to first-line PP was independently associated with a higher OR [RR 6.3, 95% CI (1.03-38.4), p = 0.046], and longer PFS [0.49 (0.25-0.9)] and OS [0.2 (0.06-0.7), p = 0.008] to second-line docetaxel compared with patients with short PFS (≤6 months) to PP. CONCLUSIONS: Previous use of PP does not preclude a favorable response to docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit from second-line docetaxel.