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1.
Adv Anat Pathol ; 31(5): 318-323, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717587

RESUMEN

The increasing incidence of multiple lung nodules underscores the need for precise differentiation between multiple primary lung cancers (MPLCs) and intrapulmonary metastases (IPMs). This distinction impacts patient prognosis and treatment strategies. The prevalence of multiple lung nodules, ranging from 19.7% to 55.5%, highlights the clinical significance of this challenge. Historically, the role of histopathology, particularly comprehensive histology assessment (CHA), has been pivotal in differentiating MPLCs and IPMs. However, CHA has significant limitations, resulting in a constant search for a better way to distinguish those lesions. The best strategy for delineating MPLCs from IPMs is a multidisciplinary approach combining clinical data, radiology, histology, and molecular methods. Histology provides architectural and cellular characteristics, radiology contributes anatomic context and lesion characterization, and molecular methods reveal molecular features critical for accurate differentiation. Incorporating clinical data further enhances diagnostic precision. This review presents current knowledge and current approaches to multiple lung tumors. It is clear that even with a combination of pathology, radiology, and molecular data, definitive classification of multifocal lung tumors is not always possible.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Diagnóstico Diferencial , Neoplasias Primarias Múltiples/patología , Biomarcadores de Tumor/análisis
2.
J Pathol ; 257(5): 674-686, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35489038

RESUMEN

The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Pronóstico , Proteómica , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/cirugía , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
3.
Am J Respir Crit Care Med ; 206(8): 981-998, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-35763380

RESUMEN

Rationale: Pulmonary hypertension (PH) is a common, severe comorbidity in interstitial lung diseases such as pulmonary fibrosis (PF), and it has limited treatment options. Excessive vascular fibrosis and inflammation are often present in PH, but the underlying mechanisms are still not well understood. Objectives: To identify a novel functional link between natural killer T (NKT) cell activation and vascular fibrosis in PF-PH. Methods: Multicolor flow cytometry, secretome, and immunohistological analyses were complemented by pharmacological NKT cell activation in vivo, in vitro, and ex vivo. Measurements and Main Results: In pulmonary vessels of patients with PF-PH, increased collagen deposition was linked to a local NKT cell deficiency and decreased IL-15 concentrations. In a mouse model of PH caused by lung fibrosis, pharmacological NKT cell activation using a synthetic α-galactosylceramide analog (KRN7000) restored local NKT cell numbers and ameliorated vascular remodeling and right ventricular systolic pressure. Supplementation with activated NKT cells reduced collagen deposition in isolated human pulmonary arterial smooth muscle cells (hPASMCs) and in ex vivo precision-cut lung slices of patients with end-stage PF-PH. Coculture with activated NKT cells induced STAT1 signaling in hPASMCs. Secretome analysis of peripheral blood mononuclear cells identified CXCL9 and CXCL10 as indicators of NKT cell activation. Pharmacologically, CXCL9, but not CXCL10, potently inhibited collagen deposition in hPASMCs via the chemokine receptor CXCR3. Conclusions: Our results indicate that the absence of NKT cells impairs the STAT1-CXCL9-CXCR3 axis in PF-PH and that restoration of this axis by NKT cell activation may unravel a novel therapeutic strategy to target vascular fibrosis in interstitial lung disease.


Asunto(s)
Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Fibrosis Pulmonar , Animales , Humanos , Ratones , Quimiocina CXCL9/uso terapéutico , Colágeno/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Interleucina-15/uso terapéutico , Leucocitos Mononucleares/metabolismo , Enfermedades Pulmonares Intersticiales/patología , Factor de Transcripción STAT1 , Células T Asesinas Naturales
4.
Emerg Infect Dis ; 28(12): 2504-2507, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36417956

RESUMEN

We report a case of human Dirofilaria repens infection in a woman in Slovenia who had concomitant pleural and subcutaneous manifestations of the infection. This case report illustrates the clinical course of a severe symptomatic parasitic infection that had multisystemic manifestations.


Asunto(s)
Dirofilaria repens , Femenino , Animales , Humanos , Eslovenia
5.
Histopathology ; 77(1): 55-66, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32170970

RESUMEN

AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. CONCLUSIONS: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.


Asunto(s)
Mesotelioma Maligno/patología , Neoplasias Pleurales/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
7.
Oncologist ; 23(12): e152-e158, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30076278

RESUMEN

This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. IMPLICATIONS FOR PRACTICE: This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Gastos en Salud/normas , Neoplasias Pulmonares/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Europa (Continente) , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Medicina de Precisión , Encuestas y Cuestionarios
8.
Radiol Oncol ; 51(3): 357-362, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28959173

RESUMEN

BACKGROUND: With introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients. PATIENTS AND METHODS: We obtained 54 surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. Results were analyzed according to cut-off values of ≥ 5% and ≥ 10% of PD-L1 expression on either TC or IC. RESULTS: 29 (54%) samples were AC and 25 (46%) were SCC. PD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. In AC alone, PD-L1 expression was significantly higher in IC compared to TC at both cut-off values (72% vs. 17%, p < 0.001 and 41% vs. 14%, p = 0.008, respectively), while no significant difference between IC and TC PD-L1 expression was revealed in SCC. CONCLUSIONS: Our results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC.

9.
Radiol Oncol ; 51(2): 195-202, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28740455

RESUMEN

BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC) in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM) status on IGF1R expression and overall survival (OS). PATIENTS AND METHODS: IGF1R expression was evaluated in 167 consecutive advanced NSCLC patients (stage IIIB and IV), diagnosed and treated at one university institution, between 2005 and 2010. All patients received at least one line of standard cytotoxic therapy and 18 of them had pre-existing T2DM. IGF1R expression was determined by immunohistochemical (IHC) staining, with score ≥ 1+ considered as positive. Information on baseline characteristics, as well as patients' follow-up data, were obtained from the hospital registry. Associations of IGF1R expression with clinical characteristics and overall survival were compared. RESULTS: IGF1R expression was positive in 79.6% of patients, significantly more often in squamous-cell carcinoma (SCC) compared to non-squamous-cell (NSCC) histology (88.7% vs. 74.3%; P = 0.03). IGF1R positivity did not correlate with T2DM status or with other clinical features (sex, smoking status, performance status). Median OS was similar between IGF1R positive and IGF1R negative group (10.2 vs. 8.5 months, P = 0.168) and between patients with or without T2DM (8.7 vs. 9.8 months, P = 0.575). Neither IGF1R expression nor T2DM were significant predictors of OS. CONCLUSIONS: IGF1R or T2DM status were not significantly prognostic in described above collective of advanced NSCLC treated with at least one line of chemotherapy. In addition, no association between T2DM status and IGF1R expression was found. Further studies on IGF1R expression and its prognostic as well as therapeutic consequences in a larger collective of advanced NSCLC patients, with or without T2DM, are needed.

10.
J Pathol ; 237(2): 203-14, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26011651

RESUMEN

Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity. Reduced expression of the novel tumour suppressor integrin α7 (ITGA7) was found in highly motile cells. A significant negative correlation was observed between ITGA7 transcript levels and average displacement of cells. Forced overexpression of ITGA7 in MPM cells with low endogenous ITGA7 expression inhibited cell motility, providing direct evidence for the regulatory role of ITGA7 in MPM cell migration. MPM cells showed decreased ITGA7 expressions at both transcription and protein levels when compared to non-malignant mesothelial cells. The majority of MPM cell cultures displayed hypermethylation of the ITGA7 promoter when compared to mesothelial cultures. A statistically significant negative correlation between ITGA7 methylation and ITGA7 expression was also observed in MPM cells. While normal human pleura samples unambiguously expressed ITGA7, a varying level of expression was found in a panel of 200 human MPM samples. In multivariate analysis, ITGA7 expression was found to be an independent prognostic factor. Although there was no correlation between histological subtypes and ITGA7 expression, importantly, patients with high tumour cell ITGA7 expression had an increased median overall survival compared to the low- or no-expression groups (463 versus 278 days). In conclusion, our data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human MPM.


Asunto(s)
Antígenos CD/metabolismo , Movimiento Celular , Epigénesis Genética , Cadenas alfa de Integrinas/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurales/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Antígenos CD/genética , Línea Celular Tumoral , Metilación de ADN , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Cadenas alfa de Integrinas/genética , Estimación de Kaplan-Meier , Laminina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mesotelioma/genética , Mesotelioma/mortalidad , Mesotelioma/patología , Mesotelioma Maligno , Análisis Multivariante , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Pleurales/genética , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Pronóstico , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , ARN Mensajero/metabolismo , Factores de Riesgo , Transducción de Señal , Factores de Tiempo , Transfección , Proteínas Supresoras de Tumor/genética
12.
Radiol Oncol ; 48(1): 67-71, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24587782

RESUMEN

BACKGROUND: Thoracoscopy with a semirigid instrument is a recent technique for diagnosing pleural diseases. The purpose of this study was to report diagnostic yield and complications of the method. PATIENTS AND METHODS: Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry with a semirigid thoracoscope (Olympus LTF-160). Data were collected prospectively between 2008 and 2012. RESULTS: One hundred fifteen thoracoscopies were performed on 111 patients. The median age was 65 years (range 28-86 years), 14.4% were female and 85.6% male. Seventy-three (65.8%) patients had malignant pleural disease (malignant mesothelioma, metastatic cancer) and 38 (34.2%) had benign disease. The sensitivity, negative predictive value, and accuracy of the procedure for malignancy were 96.0%, 93.0%, and 97.4% respectively. Pleurodesis was carried out in 34 patients; in 32 (94.1%) it was assessed as successful after 1 month. There were 24 adverse events: three empyemas/pleural infections, three bronchopleural fistulae after chest tube placement and lung re-expansion, five patients had excessive pain after pleurodesis, six patients had sedation-associated hypotension, and seven patients had self-limited fever after plerodesis. One patient died 11 days after a procedure for advanced carcinoma. CONCLUSIONS: Semirigid thoracoscopy is an accurate and safe method for evaluation of pleural diseases and useful for therapeutic talc pleurodesis.

13.
Radiol Oncol ; 48(4): 361-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25435849

RESUMEN

BACKGROUND: Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance. RESULTS: Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2-3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months. CONCLUSIONS: While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

14.
Radiol Oncol ; 48(2): 173-83, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24991207

RESUMEN

BACKGROUND: The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice. PATIENTS AND METHODS: We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival. RESULTS: Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later. CONCLUSIONS: Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

15.
Virchows Arch ; 485(2): 173-195, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39030439

RESUMEN

Occupational lung/thoracic diseases are a major global public health issue. They comprise a diverse spectrum of health conditions with complex pathology, most of which arise following chronic heavy workplace exposures to various mineral dusts, metal fumes, or following inhaled organic particulate reactions. Many occupational lung diseases could become irreversible; thus accurate diagnosis is mandatory to minimize dust exposure and consequently reduce damage to the respiratory system. Lung biopsy is usually required when exposure history is inconsistent with imaging, in case of unusual or new exposures, in case of unexpected malignancy, and in cases in which there are claims for personal injury and legal compensation. In this paper, we provide an overview of the most frequent occupational lung diseases with a focus on pathological diagnosis. This is a paper that summarizes the expert opinion from a group of European pathologists, together with contributions from other specialists who are crucial for the diagnosis and management of these diseases. Indeed, tight collaboration of all specialists involved in the workup is mandatory as many occupational lung diseases are misdiagnosed or go unrecognized. This document provides a guide for pathologists in practice to facilitate the accurate diagnosis of occupational lung disease. The review article reports relevant topics discussed during an educational course held by expert pathologists, active members of the Pulmonary Pathology Working Group of the European Society of Pathology. The course was endorsed by the University of Padova as a "winter school" (selected project in the call for "Shaping a World-class University" 2022).


Asunto(s)
Enfermedades Pulmonares , Enfermedades Profesionales , Patólogos , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/patología , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/patología , Exposición Profesional/efectos adversos , Europa (Continente) , Testimonio de Experto
16.
Lancet Reg Health Eur ; 38: 100839, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38476751

RESUMEN

For patients with advanced stage non-small cell lung cancer (NSCLC), treatment strategies have changed significantly due to the introduction of targeted therapies and immunotherapy. In the last few years, we have seen an explosive growth of newly introduced targeted therapies in oncology and this development is expected to continue in the future. Besides primary targetable aberrations, emerging diagnostic biomarkers also include relevant co-occurring mutations and resistance mechanisms involved in disease progression, that have impact on optimal treatment management. To accommodate testing of pending biomarkers, it is necessary to establish routine large-panel next-generation sequencing (NGS) for all patients with advanced stage NSCLC. For cost-effectiveness and accessibility, it is recommended to implement predictive molecular testing using large-panel NGS in a dedicated, centralized expert laboratory within a regional oncology network. The central molecular testing center should host a regional Molecular Tumor Board and function as a hub for interpretation of rare and complex testing results and clinical decision-making.

17.
Lancet Reg Health Eur ; 38: 100838, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38476742

RESUMEN

In the past two decades, the treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to the introduction of targeted therapies and immunotherapy. These advancements have led to the need for predictive molecular tests to identify patients eligible for targeted therapy. This review provides an overview of the development and current application of targeted therapies and predictive biomarker testing in European patients with advanced stage NSCLC. Using data from eleven European countries, we conclude that recommendations for predictive testing are incorporated in national guidelines across Europe, although there are differences in their comprehensiveness. Moreover, the availability of recently EMA-approved targeted therapies varies between European countries. Unfortunately, routine assessment of national/regional molecular testing rates is limited. As a result, it remains uncertain which proportion of patients with metastatic NSCLC in Europe receive adequate predictive biomarker testing. Lastly, Molecular Tumor Boards (MTBs) for discussion of molecular test results are widely implemented, but national guidelines for their composition and functioning are lacking. The establishment of MTB guidelines can provide a framework for interpreting rare or complex mutations, facilitating appropriate treatment decision-making, and ensuring quality control.

18.
Respirology ; 18(4): 704-10, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23418922

RESUMEN

BACKGROUND AND OBJECTIVE: Thoracoscopy with a semi-rigid instrument is a recent technique successfully used for diagnosing pleural diseases. However, there are concerns about the diagnostic adequacy of biopsy samples obtained by semi-rigid procedures when compared with rigid thoracoscopy. The purpose of this study was to compare the size, quality and diagnostic adequacy of biopsy specimens obtained at semi-rigid and rigid thoracoscopy in a prospective, randomized fashion. METHODS: Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry. Patients were randomly assigned to a rigid instrument procedure (Olympus EndoEYE WA50120A, forceps) or semi-rigid instrument procedure (Olympus LTF-160, FB-55CR-1 forceps). RESULTS: Eighty-four patients were randomized. Five of them were excluded because of lack of pleural space. Thirty-eight patients were assigned to a rigid and 41 to a semi-rigid procedure, with mean follow up 24.1 (±8.1) months after the procedure. The average size of the sample obtained by rigid thoracoscopy was 24.7 mm(2) (±12.9), and 11.7 mm(2) (±7.6) by semi-rigid thoracoscopy. There were no differences in the quality and interpretability of the specimens assessed by the pathologist. The diagnostic accuracy was 100% for the rigid procedure and 97.6% for the semi-rigid procedure. CONCLUSIONS: The samples obtained by semi-rigid thoracoscopy were smaller, but of adequate quality. The diagnostic accuracy was comparable with that of rigid thoracoscopy in the evaluation of pleural disease.


Asunto(s)
Enfermedades Pleurales/diagnóstico , Toracoscopía/instrumentación , Toracoscopía/métodos , Adulto , Anciano , Anestesia Local , Sedación Consciente , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Enfermedades Pleurales/patología , Estudios Prospectivos , Método Simple Ciego
19.
Cells ; 11(3)2022 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-35159182

RESUMEN

Recent studies have suggested that causative variants in telomerase complex genes (TCGs) are present in around 10% of individuals with idiopathic pulmonary fibrosis (IPF) regardless of family history of the disease. However, the studies used a case-control rare variant enrichment study design which is not directly translatable to routine practice. To validate the prevalence results and to establish the individual level, routine clinical practice, and utility of those results we performed next generation sequencing of TCGs on a cohort of well-characterized consecutive individuals with IPF (diagnosis established according to ATS/ERS/JRS/ALAT guidelines). Of 27 IPF patients, three had a family history of idiopathic interstitial pneumonia (familial IPF) and 24 did not (sporadic IPF). Pathogenic/likely-pathogenic variants (according to American College of Medical Genetics criteria) in TCG were found in three individuals (11.1%) of the whole cohort; specifically, they were present in 2 out of 24 (8.3%) of the sporadic and in 1 out of 3 (33.3%) of the patients with familial IPF. Our results, which were established on an individual-patient level study design and in routine clinical practice (as opposed to the case-control study design), are roughly in line with the around 10% prevalence of causative TCG variants in patients with IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Telomerasa , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/genética , Mutación/genética , Telomerasa/genética
20.
Radiol Oncol ; 56(3): 346-354, 2022 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-35962955

RESUMEN

BACKGROUND: Treatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I-IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010-2017. PATIENTS AND METHODS: Data of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA). RESULTS: With a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OS; but only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS. CONCLUSIONS: The study showed favourable outcomes of resectable stage I-IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos
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