Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance.

INTRODUCTION: Non-small cell lung cancer (NSCLC) patients diagnosed in early stage and surgically-treated have five-year mortality rate >20%. The identification of biomarkers able to predict progression and death may help to identify patients needing closer follow-up. METHODS: A retrospective cohort of early-stage surgically-treated NSCLC patients enrolled in the International Association for the Study of Lung Cancer (IASLC) Staging Project was created, and tissue Microarrays (TMAs) were constructed with tumor and non-tumor lung tissue. Pentose phosphate pathway (PPP) proteins (transketolase [TKT] and transketolase-like 1 [TKTL1]), inflammatory markers (cyclooxygenase-2 [COX-2], tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL1ß], nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB]-p65 and antigen Ki-67), and programmed death-ligand 1 (PDL1) were measured by immunohistochemistry. RESULTS: NSCLC patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) were included in the study (n = 199). TKT and TKTL1 were significantly higher in ADC than in non-tumor tissue (p < 0.001). Higher values were also observed in NSCLC for all the inflammatory markers, with figures >30% above those of non-tumor tissue (p < 0.001). PDL1 analysis showed a higher percentage of positivity in ADC than in non-tumor tissue (p < 0.001). Multivariate Cox proportional hazards modeling confirmed that high IL1ß level in tumor tissue was independently associated with 3-year mortality in NSCLC [HR = 2.05, 95% CI (1.1-3.7), p = 0.019], a relationship driven by ADC subtype. CONCLUSION: This study confirms an increase in metabolic activity and an inflammatory response in tumor tissue of early stage NSCLC, and a significant relationship between high levels of IL1ß in the tumor and poor prognosis in ADC.

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Análisis de marcadores biológicos en el Proyecto Estratégico de Cáncer de Pulmón CIBERES-RTIC Cáncer-SEPAR / Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer

El proyecto «Estadificación clínica y molecular del cáncer de pulmón estadios I-IIp», tiene por objetivo la identificación de variables moleculares que mejoren la capacidad pronóstica y predictiva de la clasificación TNM en el cáncer de pulmón no célula pequeña (NSCLC) estadio I/IIp. Para ello se han creado tres cohortes de pacientes de los que se recoge información clínica y muestras biológicas pulmonares y de sangre. En las muestras se validará una firma pronóstica proteica, y se analizarán micro-RNA, ALK, Ros1, Pdl-1, y niveles de expresión de TKT, TKTL1 y G6PD. Asimismo se analizarán marcadores de inflamación en tejido y marcadores de estroma. Se determinará la metilación de los genes p16, DAPK, RASSF1a, APC y CDH13 en la muestra tisular y se analizarán marcadores inflamatorios en sangre periférica. Este amplio panel analítico puede permitir la identificación de variables que mejoren la capacidad pronóstica y predictiva del TNM en el NSCLC mediante la estadificación molecular

The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp nonsmall cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel

Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer.

The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel.

Effectiveness of three sleep apnea management alternatives.

RATIONALE: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography (PSG) for diagnosis and treatment election in patients with high clinical probability of obstructive sleep apnea (OSA), but there is conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES: To determine the efficacy and cost of OSA management (diagnosis and therapeutic decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all patients (HRP arm); and (3) HRP for a subsample of patients with high clinical probability of being treated with continuous positive airway pressure (CPAP) and PSG for the remainder (elective HRP arm). METHODS: Multicentric study of 366 patients with intermediate-high clinical probability of OSA, randomly subjected to HRP and PSG. We explored the diagnostic and therapeutic decision agreements between the PSG and both HRP arms for several HRP cutoff points and calculated costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS: For equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs tended to be lower than elective HRP arm costs, and both tended to be lower than PSG arm costs if patient costs were omitted. CONCLUSION: Home respiratory polygraphy is a less costly alternative than polysomnography for the diagnosis and therapeutic decision making for patients with suspected obstructive sleep apnea. We found no advantage in cost terms, however, in using home respiratory polygraphy for all patients or home respiratory polygraphy for the most symptomatic patients and polysomnography for the rest.

Normativa SEPAR sobre estadificación del cáncer de pulmón / SEPAR Guidelines for Lung Cancer Staging

La última clasificación tumor, ganglio, metástasis (TNM), elaborada por la Asociación Internacional para elEstudio del Cáncer de Pulmón (IASLC) y basada en el análisis de pacientes procedentes de todo el mundo,introduce cambios en los descriptores, especialmente en lo referente al tamaño del tumor, y propone unanueva agrupación de estadios. También ha elaborado un nuevo mapa ganglionar que pretende facilitarla clasificación del componente «N». SEPAR recomienda utilizar esta nueva clasificación. En cuanto alos procedimientos recomendados para la estadificación, además del uso generalizado de la tomografíacomputarizada (TC), se señala el papel de la tomografía de emisión de positrones (PET) o los métodosde fusión de imágenes (PET/TC), que permiten una mejor evaluación del mediastino y de las metástasisextratorácicas. Se recomienda la incorporación de la ecobroncoscopia (EBUS) y de la ultrasonografíaesofágica (EUS), para la obtención de muestra citohistológica, en el algoritmo de estadificación y se destacala importancia de una reestadificación precisa después del tratamiento de inducción para tomar nuevasdecisiones terapéuticas. Se comenta la previsible incorporación en el futuro próximo de la estadificaciónmolecular y se recomienda la disección ganglionar sistemática con vistas a una más exacta clasificaciónquirúrgico-patológica (AU)

The latest tumour, lymph node and metastasis (TNM) classification by the International Association forthe Study of Lung Cancer (IASLC), based on the analysis of patients from all over the world, has incorporatedchanges in the descriptors, especially those regarding tumor size, while proposing new groupstaging. A new lymph node map has also been developed with the intention of facilitating the classificationof the “N” component. SEPAR recommends using this new classification. As for the proceduresrecommended for staging, in addition to the generalized use of computed tomography (CT), it pointsto the role of positron emission tomography (PET) or image fusion methods (PET/CT), which provide abetter evaluation of the mediastinum and extrathoracic metastases. Endobronchial ultrasound (EBUS)and esophageal ultrasound (EUS) for obtaining cytohistological samples have been incorporated in thestaging algorithm, and it emphasizes the importance of precise re-staging after induction treatment inorder to make new therapeutic decisions. Comment is made on the foreseeable incorporation in the nearfuture of molecular staging, and systematic lymph node dissection is recommended with the intentionof making a more exact surgical-pathological classification (AU)

SEPAR guidelines for lung cancer staging.

The latest tumour, lymph node and metastasis (TNM) classification by the International Association for the Study of Lung Cancer (IASLC), based on the analysis of patients from all over the world, has incorporated changes in the descriptors, especially those regarding tumor size, while proposing new group staging. A new lymph node map has also been developed with the intention of facilitating the classification of the "N" component. SEPAR recommends using this new classification. As for the procedures recommended for staging, in addition to the generalized use of computed tomography (CT), it points to the role of positron emission tomography (PET) or image fusion methods (PET/CT), which provide a better evaluation of the mediastinum and extrathoracic metastases. Endobronchial ultrasound (EBUS) and esophageal ultrasound (EUS) for obtaining cytohistological samples have been incorporated in the staging algorithm, and it emphasizes the importance of precise re-staging after induction treatment in order to make new therapeutic decisions. Comment is made on the foreseeable incorporation in the near future of molecular staging, and systematic lymph node dissection is recommended with the intention of making a more exact surgical-pathological classification.

Non-small cell lung cancer and silent brain metastasis. Survival and prognostic factors.

The detection of silent brain metastasis is becoming increasingly common in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate clinical course, prognostic significance, and treatment efficacy in patients with asymptomatic brain metastasis. A retrospective study of patients with cytologically and histologically diagnosed NSCLC and brain metastasis detected by cranial computed tomography or magnetic resonance imaging was performed. We compared 12 neurologically asymptomatic patients to 69 symptomatic patients and analyzed overall survival, clinical course, and prognostic factors (age, sex, performance status, histologic type, TNM stage, number and size of brain metastases, clinical neurologic status, and treatment of primary tumor and brain metastasis). The strongest favorable prognostic factor was active treatment of both the primary tumor (surgery, chemotherapy and/or thoracic radiotherapy) and brain metastasis (neurosurgery and/or whole brain radiotherapy). Neurologically asymptomatic patients had significantly longer survival times than did symptomatic patients (median survival of 7.5 and 4 months, respectively). Control of clinical neurologic status during follow-up was achieved in a greater proportion of asymptomatic patients (80%) than symptomatic patients (40%). We conclude that it is important to detect brain metastasis in patients with NSCLC before neurologic signs or symptoms develop, as early detection improves prognosis and provides patients with the opportunity of receiving timely and more effective treatment.