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Background: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Methods: Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. Results: A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma. Conclusion: Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.
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The primary objectives of the study were to analyse the robotic approach and ultrasound-guided paravertebral block compared to thoracoscopic intercostal nerve block after robotic pulmonary lobectomy on postoperative pain and opioids use. The secondary objectives were to analyse and compare patients' necessity of additional antalgic drugs and patients' performance during respiratory therapy, following robotic surgery and in the two groups. Consecutively, 52 patients undergoing robotic pulmonary lobectomies were treated either with ropivacaine-based intercostal nerve block or paravertebral block from February 2022 to October 2022. When necessary, morphine was administered at day 1. Acetaminophen was administered as an additional antalgic drug on demand up to 3 g per day. Pain was measured 1 h after the end of the surgical procedure and daily through the pain numeric rating scale (NRS). Morphine administration rate and per day and total additional administrations of acetaminophen were recorded. Pain and opioids administration was measured 1 month after the procedure. Data were analysed in the overall population and in the intercostal nerve block group VS paravertebral block group. Overall, 34.6% of the patients required morphine administration and 51.7% of the patients required at least daily acetaminophen administration up to discharge. At 1 month postoperatively, four patients presented with chronic pain and one still was under opioid medication. At intergroup analysis, the paravertebral block group demonstrated lower NRS at fixed time points (p < 0.0001) and lower morphine consumption (45.7%VS11.8%; p = 0.02). Acetaminophen rescue administration at fixed time points was lower in the paravertebral block group (p < 0.0001) and mobility and dynamic pain resulted in better results (p = 0.03; p = 0.04). At 1 month, no differences were found between study groups. Similarly to other minimally invasive techniques, postoperative pain may arise after robotic pulmonary lobectomy. Paravertebral bloc can help to reduce postoperative pain as well as morphine and antalgic drugs administration and improve early mobilization.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Dolor Postoperatorio , Procedimientos Quirúrgicos Robotizados , Proyectos Piloto , Dolor Postoperatorio/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Morfina/uso terapéutico , Acetaminofén/uso terapéutico , Analgesia , Carcinoma de Pulmón de Células no Pequeñas/cirugíaRESUMEN
BACKGROUND: Immune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC. METHODS: Mononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271). RESULTS: Transcriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients. CONCLUSIONS: Our study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Derrame Pleural Maligno , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Leucocitos Mononucleares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Macrófagos/patología , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patología , Microambiente TumoralRESUMEN
Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.
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Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Metabolismo de los Lípidos , Neoplasias Glandulares y Epiteliales/patología , ARN Largo no Codificante/genética , Neoplasias del Timo/patología , Apoptosis , Biomarcadores de Tumor/genética , Proteínas Portadoras/genética , Proteínas de Ciclo Celular/genética , Proliferación Celular , Perfilación de la Expresión Génica , Humanos , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Pronóstico , Tasa de Supervivencia , Neoplasias del Timo/genética , Neoplasias del Timo/metabolismo , Células Tumorales CultivadasAsunto(s)
COVID-19 , Cirugía Torácica , Prueba de COVID-19 , Hospitales , Humanos , Pandemias , Estándares de Referencia , SARS-CoV-2RESUMEN
Among the group of thymic epithelial tumors (TET), thymomas often show either uncertain or explicit malignant biological behavior, local invasiveness, and intrathoracic relapse and are often difficult to manage. From the initial stages, thymic carcinomas tend to show aggressive behavior and extrathoracic spread. Moreover, the interplay of epithelial cells and thymocytes in thymomas causes complex immune derangement and related systemic autoimmune diseases. Due to their rare occurrence and to the limited funding opportunities available for rare tumors, it is challenging to make advances in clinical and translational research in TET. The authors of this paper are all members of a multidisciplinary clinical and research thoracic tumor team. Strong input was given to the team by long-standing expertise in TET in the Pathology Department. In addition, thanks to the collaboration between research units at our Institute as well as to national collaborations, over the last 10 years we were able to perform several tissue-based research studies. The most recent studies focused on microRNA and on functional studies on the thymic carcinoma cell line 1889c. The recent implementation of our biobank now provides us with a new tool for networking collaborative research activities. Moreover, the participation in a worldwide community such as ITMIG (International Thymic Malignancy Interest Group) has allowed us to significantly contribute toward fundamental projects/research both in tissue-based studies (The Cancer Genome Atlas) and in clinical studies (TNM staging of TET). Our achievements derive from constant commitment and long-standing experience in diagnosis and research in TET. New perspectives opened up due to the establishment of national [the Italian Collaborative Group for ThYmic MalignanciEs (TYME)] and European reference networks such as EURACAN, for an empowered joint clinical action in adult solid rare tumors. The challenge we face still lies in the advancement of clinical and basic science in thymic epithelial malignancies.
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Isolated endobronchial tumors of the left main bronchus are quite rare. They are treated by surgical resection, preferably using lung-sparing techniques, when possible. These procedures are technically challenging and are usually performed through a standard thoracotomy. This video tutorial shows a left main bronchus sleeve resection with distal lobar carina reconstruction, performed through a uniportal thoracoscopic approach, for a typical carcinoid tumor of the distal left main bronchus.
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Neoplasias de los Bronquios , Tumor Carcinoide , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Adulto , Bronquios/patología , Bronquios/cirugía , Neoplasias de los Bronquios/patología , Neoplasias de los Bronquios/cirugía , Tumor Carcinoide/patología , Tumor Carcinoide/cirugía , Humanos , Masculino , Tratamientos Conservadores del Órgano/métodos , Procedimientos de Cirugía Plástica/métodos , Resultado del TratamientoRESUMEN
Cancer stem cells (CSCs) are a subpopulation with the properties of extensive self-renewal, capability to generate differentiated cancer cells and resistance to therapies. We have previously shown that malignant pleural effusions (MPEs) from patients with non-small-cell lung cancer (NSCLC) represent a valuable source of cancer cells that can be grown as three-dimensional (3D) spheroids enriched for stem-like features, which depend on the activation of the Yes-associated protein-transcriptional coactivator with PDZ-binding motif (YAP-TAZ)/Wnt-ßcatenin/stearoyl-CoA desaturase 1 (SCD1) axis. Here, we describe a novel support, called CytoMatrix, for the characterization of limited amounts of cancer cells isolated from MPEs of patients with NSCLC. Our results show that this synthetic matrix allows an easy and fast characterization of several epithelial cellular markers. The use of CytoMatrix to study CSCs subpopulation confirms that SCD1 protein expression is enhanced in 3D spheroids when compared with 2D adherent cell cultures. YAP/TAZ nuclear-cytoplasmic distribution analysed by CytoMatrix in 3D spheroids is highly heterogeneous and faithfully reproduces what is observed in tumour biopsies. Our results confirm and extend the robustness of our workflow for the isolation and phenotypic characterization of primary cancer cells derived from the lung MPEs and underscore the role of SCD1.
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Citodiagnóstico/métodos , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/patología , Derrame Pleural Maligno/patología , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Técnicas de Cultivo de Célula/métodos , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Femenino , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Derrame Pleural Maligno/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Estearoil-CoA Desaturasa/metabolismo , Factores de Transcripción/metabolismo , Células Tumorales CultivadasRESUMEN
Adaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP). Thus, administration of a clinical trial grade, HSP90, inhibitor blunted the release of several cytokines by the chemotherapy-treated MPM cells, including interleukin (IL)-8. Reduction of IL-8 levels hampered the FAK-AKT signaling and inhibited 3D growth and migration. This correlated with downregulation of key EMT and chemoresistance genes and affected the survival of chemoresistant ALDHbright cell subpopulations. Altogether, inhibition of HSP90 provoked a switch from a pro-tumorigenic SASP to a pro-apoptotic senescence status, thus resulting in chemosensitizing effects. In mouse xenografts treated with first-line agents, inhibiting HSP90 blunted FAK activation and reduced the expression of ALDH1A3 and the levels of circulating human IL-8, these latter strongly correlating with the effect on tumor growth. We validated the above findings in primary mesothelioma cultures, a more clinically relevant model. We unveiled here a key contribution of the chaperone HSP90 at assisting the secretory stress in chemotherapy-treated cells, which may warrant further investigation in combinatorial therapeutic settings.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Vías Secretoras/efectos de los fármacos , Triazoles/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Senescencia Celular/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/genética , Mesotelioma Maligno , Ratones , Ratones Endogámicos NOD , Ratones SCID , Pemetrexed/farmacología , Vías Secretoras/genéticaRESUMEN
By using human melanoma and glioblastoma cell lines and their derivative BCL-XL overexpressing clones, we investigated the role of BCL-XL in aggressive features of these two tumor histotypes. We found that in both models, BCL-XL overexpression increased in vitro cell migration and invasion and facilitated tumor cells to form de novo vasculogenic structures. Furthermore, BCL-XL overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-XL plays essential roles in the maintenance of cancer stem cell phenotype. BCL-XL expression reduction by siRNA, the exposure to a BCL-XL-specific inhibitor and the use of a panel of human melanoma cell lines corroborated the evidence that BCL-XL regulates tumor progression-associated properties. Finally, the vascular markers and the vasculogenic mimicry were up-regulated in the BCL-XL overexpressing xenografts derived from both tumor histotypes. In conclusion, our work brings further support to the understanding of the malignant actions of BCL-XL and, in particular, to the concept that BCL-XL promotes stemness and contributes to the aggressiveness of both melanoma and glioblastoma.
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Neoplasias Encefálicas/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Melanoma/genética , Neovascularización Patológica/genética , Neoplasias Cutáneas/genética , Proteína bcl-X/genética , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Desnudos , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Transducción de Señal , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Tiazolidinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína bcl-X/antagonistas & inhibidores , Proteína bcl-X/metabolismoRESUMEN
Background Despite the intense debate concerning management of advanced thymic tumors, no specific oncological strategies have been yet recommended. We report our 13 years' experience to investigate this issue. Methods From 01/2001 to 12/2013, the clinical data of 28 patients treated for Masaoka stages III-IV thymic tumors were retrospectively reviewed. Eleven potentially nonresectable patients (Group A) underwent induction chemotherapy plus surgery, while immediate surgery was performed in 17 patients (Group B). The endpoint was to compare the two groups on (1) surgical resectability; (2) postoperative course; (3) disease-free survival; and (4) overall survival. Results Both groups were comparable in terms of age, gender, clinical stage, clinical tumor size, histology, and adjuvant therapy. Length of surgery was statistically longer in Group A (p = 0.015). Combined surgery and R0 resection was similarly performed in both groups (p = 0.14 and p = 0.99, respectively). The 3-year overall survival was 71.4% for Group A and 93.3% for Group B (p = 0.84). On the other hand, 3-year disease-free survival was 40.5 and 53.7% for Group A and B, respectively (p = 0.67). At multivariate analysis, gender was the strongest predictor for recurrence (hazard ratio = 5.71 [1.22; 26.67], p = 0.03). Conclusion Our results suggest that induction therapy allows obtaining acceptable clinical responses as well as resectability, survival, and recurrence rates. In selected patients with "clinically resectable" stage III-IV cancers, surgery (as first step of a multimodality therapy) could be a feasible treatment option.
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Quimioterapia de Inducción , Terapia Neoadyuvante , Timectomía , Neoplasias del Timo/terapia , Adulto , Anciano , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Tempo Operativo , Complicaciones Posoperatorias/etiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Timectomía/efectos adversos , Timectomía/mortalidad , Neoplasias del Timo/mortalidad , Neoplasias del Timo/patología , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Adulto JovenRESUMEN
OBJECTIVE: Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed. METHODS: From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method. RESULTS: Overall, median OS, CSS, and RFS were 29 (95 % CI 18-39), 48 (95 % CI 19-78), and 22 (95 % CI 17-27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21-7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00-1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95-6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88-3.88, p = 0.10) experienced a worse RFS. CONCLUSIONS: In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.
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Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neumonectomía , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Carga TumoralRESUMEN
BACKGROUND: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. METHODS: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. RESULTS: A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. CONCLUSIONS: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.
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Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Mama/genética , Centrosoma/metabolismo , Mutación de Línea Germinal , Proteína p53 Supresora de Tumor/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Proteína BRCA2/genética , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Humanos , Persona de Mediana Edad , MitosisRESUMEN
BACKGROUND: Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. METHODS: From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. RESULTS: Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001). CONCLUSIONS: Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.