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1.
Virchows Arch ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39354109

RESUMEN

Despite advancements in precision medicine, many cancer patients globally, particularly those in resource-constrained environments, face significant challenges in accessing high-quality molecular testing and targeted therapies. The considerable heterogeneity in molecular testing highlights the urgent need to harmonize practices across Europe and beyond, establishing a more standardized and consistent approach in MP laboratories. Professionals, especially molecular pathologists, must move beyond traditional education to cope with this heterogeneity. This perspective addresses critical issues in molecular pathology (MP), such as limited access to high-quality molecular testing, leading to disparities in cancer treatment, and the consequences of inconsistent practices. Recognizing the necessity for a standardized framework for education to address these issues, educational programs play a pivotal role in updating professionals' skills to achieve standardization in MP. European experts from the Steering Committee, the Pathology Section of the European Union of Medical Specialists, and the European Society of Pathology have proposed creating a comprehensive Master's degree program called the "European Masters in Molecular Pathology" (EMMP). This program emerges as a strategic response to the demand for a specialized and standardized framework for education in MP, catering to professionals who concurrently work and study. The program's design aligns with evidence-based education methods, ensuring effective learning and engagement while integrating computational pathology to analyze complex molecular data, enhance diagnostic accuracy, and improve treatment outcomes. EMMP's structured curriculum, strategic partnerships, and regular updates underscore its significance in standardizing MP practices. Exploring future developments, this perspective delves into technology integration and interdisciplinary collaboration, anticipating ongoing advances and harmonization. Challenges and future directions in MP education are discussed, emphasizing the necessity for dynamic curriculum updates, seamless technology integration, and interdisciplinary cooperation. This perspective underscores EMMP's pivotal role in preparing pathologists for this dynamic field, advocating continuous advancements in education and training to uphold excellence in MP practices and maintain the highest patient care standards.

2.
Cancers (Basel) ; 16(19)2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39409962

RESUMEN

The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more personalized and effective treatment options. However, most studies into the lung microbiota have been observational and have not adequately considered the impact of dietary intake and air pollutants. This gap makes it challenging to establish a direct causal relationship between environmental exposure, changes in the composition of the microbiota, lung carcinogenesis, and tumor progression. A holistic understanding of the lung microbiota that considers both diet and air pollutants may pave the way to improved prevention and management strategies for lung cancer.

3.
Cancers (Basel) ; 16(19)2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39409960

RESUMEN

The targeted therapies and immunotherapies in thoracic oncology, particularly for NS-NSCLC, are associated with an increase in the number of predictive biomarkers to be assessed in routine clinical practice. These treatments are administered thanks to marketing authorization for use in daily practice or are evaluated during clinical trials. Since the molecular targets to be identified are more and more complex and numerous, it is now mandatory to use NGS. NGS can be developed from both tissue and fluid (mainly blood). The blood tests in oncology, so-called "liquid biopsies" (LB), are performed with plasmatic circulating free DNA (cf-DNA) and are complementary to the molecular testing performed with a TB. LB use in lung cancer is associated with international guidelines, but additional algorithms could be set up. However, even if useful for better care of patients, notably with advanced and metastatic NS-NSCLC, until now LB are not often integrated into daily practice, at least in Europe and notably in France. The purpose of this review is to describe the different opportunities and algorithms leading to the identification of the molecular signature of NS-NSCLC, using both tissue and liquid biopsies, and to introduce the principle limitations but also some perspectives in this field.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39213311

RESUMEN

INTRODUCTION: Partial androgen insensitivity syndrome (PAIS) is a rare condition that is reported to be commonly associated with gynecomastia in males. OBJECTIVES: To assess the management of gynecomastia in male PAIS. MATERIALS AND METHODS: Retrospective review of males with PAIS over the age of 10 years in the I-DSD registry. RESULTS: Of the 205 eligible cases, information was available for 57 from 13 centers. An androgen receptor gene variant was confirmed in 45 (79%) with a median age at first presentation of 1.0 year (range 0.1, 26.0). Of the 45 genetically confirmed cases, gynecomastia was present in 41 (91%) with a median age at the time of gynecomastia development of 13.5 years (11.0, 29.0). In the other 4 (9%) with no gynecomastia, the median age at last assessment was 15.7 years (10.6, 17.0). In 30 cases with information available, micropenis was present at the time of gynecomastia development in 23 (77%). Of the 35 with information available, 2 (6%) exhibited spontaneous resolution between the ages of 15 and 21 years and 25 (71%) had breast surgery at a median age of 15.7 years (14.0, 23.0). Of these 25, 9 (26%) had previously received medical therapy. The median clinician score of effectiveness for medical therapy was 3 (1, 8) compared to 10 (3, 10) for surgery (P < .0001). In 31 with information available, 13 (42%) had received psychology support. CONCLUSION: Gynecomastia is common in PAIS but not universal. Surgical management may be more effective than medical therapy, but there is a need for further standardized and systematic studies.

5.
Diagnosis (Berl) ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088796

RESUMEN

OBJECTIVES: This paper aims to identify and address gaps in cancer treatment and diagnosis within European health services, focusing specifically on discrepancies between clinical guidelines and policy guidelines. It seeks to highlight how the underutilization of advanced diagnostic techniques recommended by medical societies contributes to missed opportunities for improving patient outcomes. METHODS: A comprehensive analysis was conducted across multiple European countries to assess the compliance and integration of clinical guidelines with the availability of advanced diagnostic technologies. Secondary data related to clinical and policy guidelines in cancer care were collected and analyzed. Key indicators of adoption and utilization of next-generation sequencing and liquid biopsy were examined to evaluate their impact on health service efficiency and patient care. RESULTS: The analysis revealed significant discrepancies between the recommendations of medical societies regarding advanced diagnostic techniques and their adoption in health policy decisions across Europe. Country-specific assessments indicated varying levels of alignment between clinical guidelines and the availability of advanced diagnostics. These findings underscored missed opportunities for optimizing patient care and health service efficiency through better alignment and integration of clinical guidelines with policy decisions. CONCLUSIONS: This study concludes that there is a critical need for health policy decision-makers to prioritize the adoption of clinical guidelines in resource allocation and health service organization. Greater attention to the recommendations of medical societies regarding advanced diagnostic techniques could significantly enhance diagnostic accuracy, treatment efficacy, and overall patient outcomes in cancer care. The paper advocates for policy reforms that acknowledge and leverage the potential benefits of advanced diagnostics in improving health service performance and patient-centered care across Europe.

6.
Seizure ; 121: 105-113, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39146706

RESUMEN

INTRODUCTION: Periventricular nodular heterotopias (PVNH) are developmental abnormalities with neurons abnormally clustered around the cerebral ventricles. Patients frequently present with focal drug-resistant epilepsy (DRE). However, the relationship between PVNH and the seizure onset zone (SOZ) is complex. Stereo-electroencephalography (SEEG) is an invasive diagnostic procedure for patients with DRE. In selected patients, the SEEG may be converted into a therapeutic procedure, lesioning the probable (SOZ) with pulsed radiofrequency thermocoagulation (RFTC). The aim of our study was to evaluate the efficacy and safety of SEEG-RFTC in a series of DRE patients with PVNH. METHODS: Twenty-four patients with focal DRE related to PVNH and treated with SEEG-guided-RFTC restricted to nodules were prospectively collected between 2016 and 2023 and retrospectively analyzed after a follow-up of at least 12 months. RESULTS: Seventeen patients (71 %) responded (ILAE class 1-4) after SEEG-guided RFTC of whom eleven (46 %) became seizure-free (class 1) at last follow up, nine (45 %) despite residual PVNH tissue on MRI. SEEG seizure onset was restricted to PVNH in eleven patients (class 1 in 45 %) and simultaneously in PVNH and other cortical areas in thirteen patients (class 1 in 46 %). Out of 31 SEEG-RFTC procedures in twenty-four patients, adverse events, related to RFTC, were recorded in eight (26 %), of which two patients (8 %) had predicted permanent visual complaints whilst the other five had transient complaints. SIGNIFICANCE: This study demonstrates that a considerable percentage of patients, even with bilateral, multiple PVNH and involvement of adjacent cortical regions can be rendered seizure-free with SEEG-guided-RFTC restricted to the nodules. Furthermore, this study delivers evidence that the complete destruction of the entire nodule is not necessary to render a patient seizure free. This justifies the use of SEEG in patients with single, multiple or bilateral PVNHs to provide insight into the epileptogenic organization in and around these lesions.


Asunto(s)
Epilepsia Refractaria , Electrocoagulación , Electroencefalografía , Heterotopia Nodular Periventricular , Técnicas Estereotáxicas , Humanos , Electroencefalografía/métodos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/terapia , Masculino , Femenino , Adulto , Electrocoagulación/métodos , Adulto Joven , Heterotopia Nodular Periventricular/complicaciones , Adolescente , Estudios Retrospectivos , Persona de Mediana Edad , Niño , Resultado del Tratamiento , Imagen por Resonancia Magnética , Estudios de Seguimiento
7.
Am J Surg Pathol ; 48(9): 1072-1081, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38980727

RESUMEN

Emerging therapies for non-small cell lung cancer targeting c-Met overexpression have recently demonstrated promising results. However, the evaluation of c-Met expression can be challenging. We aimed to study the inter and intraobserver reproducibility of c-Met expression evaluation. One hundred ten cases with non-small cell lung cancer (40 biopsies and 70 surgical specimens) were retrospectively selected in a single laboratory (LPCE) and evaluated for c-Met expression. Six pathologists (4 seniors and 2 juniors) evaluated the H-score and made a 3-tier classification of c-Met expression for all cases, using conventional light microscopy (CLM) and whole slide imaging (WSI). The interobserver reproducibility with CLM gave global Cohen Kappa coefficients (ƙ) ranging from 0.581 (95% CI: 0.364-0.771) to 0.763 (95% CI: 0.58-0.92) using the c-Met 3-tier classification and H-score, respectively. ƙ was higher for senior pathologists and biopsy samples. The interobserver reproducibility with WSI gave a global ƙ ranging from 0.543 (95% CI: 0.33-0.724) to 0.905 (95% CI: 0.618-1) using the c-Met H-score and 2-tier classification (≥25% 3+), respectively. ƙ for intraobserver reproducibility between CLM and WSI ranged from 0.713 to 0.898 for the c-Met H-score and from 0.600 to 0.779 for the c-Met 3-tier classification. We demonstrated a moderate to excellent interobserver agreement for c-Met expression with a substantial to excellent intraobserver agreement between CLM and WSI, thereby supporting the development of digital pathology. However, some factors (scoring method, type of tissue samples, and expertise level) affect reproducibility. Our findings highlight the importance of establishing a consensus definition and providing further training, particularly for inexperienced pathologists, for c-Met immunohistochemistry assessment in clinical practice.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Inmunohistoquímica , Neoplasias Pulmonares , Microscopía , Variaciones Dependientes del Observador , Proteínas Proto-Oncogénicas c-met , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas Proto-Oncogénicas c-met/análisis , Proteínas Proto-Oncogénicas c-met/metabolismo , Reproducibilidad de los Resultados , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/química , Biomarcadores de Tumor/análisis , Estudios Retrospectivos , Masculino , Femenino , Valor Predictivo de las Pruebas , Biopsia , Anciano
9.
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
10.
Crit Rev Oncol Hematol ; 201: 104433, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38955310

RESUMEN

If Europe's health systems make a conscious decision to increase their utilization of technology and techniques that can enhance prevention and expedite early-stage diagnosis, they can effectively address the growing challenges of disease. By embracing these advancements, these health systems can significantly improve their response to emerging health issues.However, at present the effective integration and exploitation of these opportunities remains hesitant and suboptimal, and health and health services underperform accordingly, with patients suffering from the continuing variations in diagnosis and access to innovation. This paper presents a comprehensive study that examines the current state of various influential disciplines and factors in European countries. It specifically focuses on the adoption of Next Generation Screening technologies and the development stage of Public Health Genomics. The assessment of these areas is presented in the context of a rapidly changing policy environment, which provides an opportunity for a fundamental reconsideration of how and where new tools can be integrated into healthcare systems and routine practices. Top of Form.


Asunto(s)
Atención a la Salud , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Salud Pública , Humanos , Genómica/métodos , Salud Pública/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
11.
Front Endocrinol (Lausanne) ; 15: 1257888, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974579

RESUMEN

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.


Asunto(s)
Medios de Contraste , Histerosalpingografía , Yodo , Índice de Embarazo , Humanos , Femenino , Yodo/orina , Yodo/deficiencia , Adulto , Histerosalpingografía/métodos , Estudios Prospectivos , Embarazo , Infertilidad Femenina/epidemiología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Fertilidad/efectos de los fármacos , Nueva Zelanda/epidemiología , Aceites , Estudios de Cohortes , Pruebas de Función de la Tiroides
12.
Cancers (Basel) ; 16(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38927925

RESUMEN

The identification of ALK fusions in advanced non-small-cell lung carcinoma (aNSCLC) is mandatory for targeted therapy. The current diagnostic approach employs an algorithm using ALK immunohistochemistry (IHC) screening, followed by confirmation through ALK FISH and/or next-generation sequencing (NGS). Challenges arise due to the infrequency of ALK fusions (3-7% of aNSCLC), the suboptimal specificity of ALK IHC and ALK FISH, and the growing molecular demands placed on small tissue samples, leading to interpretative, tissue availability, and time-related issues. This study investigates the effectiveness of RNA NGS as a reflex test for identifying ALK fusions in NSCLC, with the goal of replacing ALK IHC in the systematic screening process. The evaluation included 1246 NSCLC cases using paired techniques: ALK IHC, ALK FISH, and ALK NGS. ALK IHC identified 51 positive cases (4%), while RNA NGS detected ALK alterations in 59 cases (4.8%). Of the 59 ALK-positive cases identified via NGS, 53 (89.8%) were confirmed to be positive. This included 51 cases detected via both FISH and IHC, and 2 cases detected only via FISH, as they were completely negative according to IHC. The combined reporting time for ALK IHC and ALK FISH averaged 13 days, whereas ALK IHC and RNA NGS reports were obtained in an average of 4 days. These results emphasize the advantage of replacing systematic ALK IHC screening with RNA NGS reflex testing for a more comprehensive and accurate assessment of ALK status.

13.
Cancers (Basel) ; 16(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38927931

RESUMEN

The aim of this study was to assess the potential value of circulating active and inactive IL-18 levels in distinguishing pseudo and true tumor progression among NSCLC patients receiving immune checkpoint inhibitor treatments (ICIs). METHODS: This ancillary study includes 195 patients with metastatic non-small-cell lung cancer (NSCLC) treated with ICI in monotherapy, either pembrolizumab or nivolumab. Plasmatic levels of IL-18-related compounds, comprising the inhibitor IL-18 binding protein (IL-18BP), the inactive IL-18 (corresponding to IL-18/IL-18BP complex), and the active free IL-18, were assayed by ELISA. Objective tumoral response was analyzed by 18FDG PET-CT at baseline, 7 weeks, and 3 months post treatment induction, using PERCIST criteria. RESULTS: Plasmatic IL-18BP and total IL-18 levels are increased at baseline in NSCLC patients compared with healthy controls, whereas IL-18/IL-18BP complexes are decreased, and free IL-18 levels remain unchanged. Neither of the IL-18-related compounds allowed to discriminate ICI responding to nonresponding patients. However, inactive IL-18 levels allowed to discriminate patients with a first tumor progression, assessed after 7 weeks of treatment, with worse overall survival. In addition, we showed that neutrophil concentration is also a predictive indicator of patients' outcomes with OS (HR = 2.6, p = 0.0001) and PFS (HR = 2.2, p = 0.001). CONCLUSIONS: Plasmatic levels of inactive IL-18, combined with circulating neutrophil concentrations, can effectively distinguish ICI nonresponding patients with better overall survival (OS), potentially guiding rapid decisions for therapeutic intensification.

14.
Transl Lung Cancer Res ; 13(5): 1150-1162, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38854939

RESUMEN

Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease. Case Description: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery. Conclusions: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.

15.
J Clin Oncol ; 42(27): 3183-3186, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38935877

RESUMEN

Navigating change in tumor naming. Balance organ-based and molecular classifications for optimal treatment.


Asunto(s)
Neoplasias , Terminología como Asunto , Humanos , Neoplasias/genética , Neoplasias/clasificación , Neoplasias/patología , Neoplasias/terapia
16.
Front Immunol ; 15: 1384121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903504

RESUMEN

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.


Asunto(s)
Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Microambiente Tumoral , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Resistencia a Antineoplásicos/inmunología , Microambiente Tumoral/inmunología , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Animales , Inmunoterapia/métodos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología
17.
J Med Imaging (Bellingham) ; 11(3): 037502, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38737491

RESUMEN

Purpose: Immune checkpoint inhibitors (ICIs) are now one of the standards of care for patients with lung cancer and have greatly improved both progression-free and overall survival, although <20% of the patients respond to the treatment, and some face acute adverse events. Although a few predictive biomarkers have integrated the clinical workflow, they require additional modalities on top of whole-slide images and lack efficiency or robustness. In this work, we propose a biomarker of immunotherapy outcome derived solely from the analysis of histology slides. Approach: We develop a three-step framework, combining contrastive learning and nonparametric clustering to distinguish tissue patterns within the slides, before exploiting the adjacencies of previously defined regions to derive features and train a proportional hazards model for survival analysis. We test our approach on an in-house dataset of 193 patients from 5 medical centers and compare it with the gold standard tumor proportion score (TPS) biomarker. Results: On a fivefold cross-validation (CV) of the entire dataset, the whole-slide image-based survival analysis for patients treated with immunotherapy (WhARIO) features are able to separate a low- and a high-risk group of patients with a hazard ratio (HR) of 2.29 (CI95=1.48 to 3.56), whereas the TPS 1% reference threshold only reaches a HR of 1.81 (CI95=1.21 to 2.69). Combining the two yields a higher HR of 2.60 (CI95=1.72 to 3.94). Additional experiments on the same dataset, where one out of five centers is excluded from the CV and used as a test set, confirm these trends. Conclusions: Our uniquely designed WhARIO features are an efficient predictor of survival for lung cancer patients who received ICI treatment. We achieve similar performance to the current gold standard biomarker, without the need to access other imaging modalities, and show that both can be used together to reach even better results.

18.
J Clin Pathol ; 77(7): 457-463, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38702192

RESUMEN

AIMS: A mutation in the SMARCA4 gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis. SMARCA4 mutations are present in approximately 10% of non-small cell lung cancers (NSCLC), making it a crucial gene in NSCLC, but with varying prognostic associations. To explore this, we conducted a systematic review and meta-analysis on the prognostic significance of SMARCA4 mutations in NSCLC. METHODS: Electronic database search was performed from inception to December 2022. Study characteristics and prognostic data were extracted from each eligible study. Depending on heterogeneity, pooled HR and 95% CI were derived using the random-effects or fixed-effects models. RESULTS: 8 studies (11 cohorts) enrolling 8371 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 8 (10 cohorts) and 1 (3 cohorts) studies, respectively. Comparing SMARCA4-mutated NSCLC patients with SMARCA4-wild-type NSCLC patients, the summary HRs for OS and PFS were 1.49 (95% CI 1.18 to 1.87; I2=84%) and 3.97 (95% CI 1.32 to 11.92; I2=79%), respectively. The results from the trim-and-fill method for publication bias and sensitivity analysis were inconsistent with the primary analyses. Three studies reported NSCLC prognosis for category I and II mutations separately; category I was significantly associated with OS. CONCLUSION: Our findings suggest that SMARCA4 mutation negatively affects NSCLC OS and PFS. The prognostic effects of SMARCA4-co-occurring mutations and the predictive role of SMARCA4 mutation status in immunotherapy require further exploration.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , ADN Helicasas , Neoplasias Pulmonares , Mutación , Proteínas Nucleares , Factores de Transcripción , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , ADN Helicasas/genética , Factores de Transcripción/genética , Proteínas Nucleares/genética , Pronóstico , Biomarcadores de Tumor/genética
20.
Curr Oncol ; 31(4): 1839-1864, 2024 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-38668042

RESUMEN

Understanding the diversity in cancer research priorities and the correlations among different treatment modalities is essential to address the evolving landscape of oncology. This study, conducted in collaboration with the European Cancer Patient Coalition (ECPC) and Childhood Cancer International-Europe (CCI-E) as part of the "UNCAN.eu" initiative, analyzed data from a comprehensive survey to explore the complex interplay of demographics, time since cancer diagnosis, and types of treatments received. Demographic analysis revealed intriguing trends, highlighting the importance of tailoring cancer research efforts to specific age groups and genders. Individuals aged 45-69 exhibited highly aligned research priorities, emphasizing the need to address the unique concerns of middle-aged and older populations. In contrast, patients over 70 years demonstrated a divergence in research priorities, underscoring the importance of recognising the distinct needs of older individuals in cancer research. The analysis of correlations among different types of cancer treatments underscored the multidisciplinary approach to cancer care, with surgery, radiotherapy, chemotherapy, precision therapy, and biological therapies playing integral roles. These findings support the need for personalized and combined treatment strategies to achieve optimal outcomes. In conclusion, this study provides valuable insights into the complexity of cancer research priorities and treatment correlations in a European context. It emphasizes the importance of a multifaceted, patient-centred approach to cancer research and treatment, highlighting the need for ongoing support, adaptation, and collaboration to address the ever-changing landscape of oncology.


Asunto(s)
Neoplasias , Humanos , Neoplasias/terapia , Masculino , Anciano , Persona de Mediana Edad , Femenino , Investigación Biomédica , Adulto , Demografía , Investigación , Europa (Continente)
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