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BACKGROUND: Lung cancers represent the main cause of cancer related-death worldwide. Recently, immunotherapy alone or in combination with chemotherapy has deeply impacted the therapeutic care leading to an improved overall survival. However, relapse will finally occur, with no efficient second line treatment so far. New therapies development based on the comprehension of resistance mechanisms is necessary. However, the difficulties to obtain tumor samples before and after first line treatment hamper to clearly understand the consequence of these molecules on tumor cells and also to identify adapted second line therapies. METHODS: To overcome this difficulty, we developed multicellular tumor spheroids (MCTS) using characterized Non-Small Cell Lung Cancer (NSCLC) cell lines, monocytes from healthy donors and fibroblasts. MCTS were treated with carboplatin-paclitaxel or -gemcitabine combinations according to clinical administration schedules. The treatments impact was studied using cell viability assay, histological analyses, 3'RNA sequencing, real-time PCR, flow cytometry and confocal microscopy. RESULTS: We showed that treatments induced a decrease in cell viability and strong modifications in the transcriptomic profile notably at the level of pathways involved in DNA damage repair and cell cycle. Interestingly, we also observed a modification of genes expression considered as hallmarks of response to immune check point inhibitors and immunogenicity, particularly an increase in CD274 gene expression, coding for PD-L1. This result was validated at the protein level and shown to be restricted to tumor cells on MCTS containing fibroblasts and macrophages. This increase was also observed in an additional cell line, expressing low basal CD274 level. CONCLUSIONS: This study shows that MCTS are interesting models to study the impact of first line therapies using conditions close to clinical practice and also to identify more adapted second line or concomitant therapies for lung cancer treatment.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia , Esferoides Celulares , Paclitaxel/uso terapéutico , Antígeno B7-H1RESUMEN
INTRODUCTION: The number of Advanced Practice Nurses (APNs) has significantly increased in France since 2019, with the number of graduates expected to reach 1700 by the end of 2023, up from approximately 60. Fifteen percent of them specialize in oncology-hematology (APN-OH). Data on their activities, access to continuing education, and expectations are limited. METHODS: We conducted an observational study among practicing APN-OHs in France. A questionnaire was distributed from June to September 2023. RESULTS: Of the 55 responding APN-OHs, 78.3% worked in Cancer Centers or within University Hospital Centers. Their primary motivation for becoming APN-OH was to enhance their nursing practice and deepen their medical knowledge, with teaching and research interests remaining marginal. Their level of responsibility generally aligned with their expectations and the medical staff was perceived as supportive. The main challenges were of logistical and material nature. The heterogeneity in APN-OH training was seen as a limiting factor in the attractiveness of the profession. The most significant gaps in their education revolved around the lack of practical cases. CONCLUSION: This study highlights that the primary concern of APN-OHs is to strengthen their practical training. Medical personnel are perceived as supportive, but challenges related to working conditions and education persist. It is essential to consider these factors to support the deployment of APN-OHs across the country and improve ongoing education.
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Enfermería de Práctica Avanzada , Educación Continua en Enfermería , Hematología , Enfermería Oncológica , Humanos , Francia , Enfermería Oncológica/educación , Femenino , Masculino , Enfermería de Práctica Avanzada/educación , Hematología/educación , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto , Motivación , Instituciones Oncológicas , Actitud del Personal de SaludRESUMEN
Serum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations.
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Neoplasias del Colon , Fluorodesoxiglucosa F18 , Anciano , Calcitonina , Antígeno Carcinoembrionario , Neoplasias del Colon/diagnóstico por imagen , Humanos , Masculino , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Glándula TiroidesRESUMEN
INTRODUCTION: The high frequency of RAS mutations, particularly KRAS mutations, in colorectal cancer (CRC) and the ineffectiveness of anti-EGFR antibodies in treating this disease has created a significant unmet medical need, especially for treating patients in the metastatic phase of this disease. There are many different types of RAS mutations, the most frequent being G12V (c.35 G > T (p.G12V)), G12D (c.35 G > A (p.G12D)), and G13D (c.38 G > A (p.G13D)). Here, we provide an overview of RAS mutations in CRC and their therapeutic implications. AREAS COVERED: The therapeutic strategies against metastatic CRC with RAS mutations are elaborated according to patient and disease characteristics and integrated into a multiline strategy. The complexity of the molecular structure of RAS and its relationship with the MAPK/ERK pathway partly explain the initial therapeutic failure with MEK or farnesyltransferase inhibitors. Conversely, the development of direct KRAS inhibitors or drugs targeting RAS regulators (e.g. SOS1 and SHP2) has opened new therapeutic fields, requiring the distinction of each KRAS mutation type. EXPERT OPINION: In the future, KRAS inhibitors, including SOS1 and SHP2 inhibitors, might be used in combination with other signal transduction inhibitors, such as MEK inhibitors or anti-EGFR antibodies, which block alternative pathways of activation.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras) , Biomarcadores de Tumor , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Mutación , Medicina de Precisión , Proteínas Proto-Oncogénicas p21(ras)/genéticaAsunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Infecciones por Citomegalovirus/inmunología , Gastritis/inmunología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Úlcera Gástrica/inmunología , Adulto , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inducido químicamente , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/inmunología , Mucosa Gástrica/patología , Gastritis/inducido químicamente , Gastritis/diagnóstico , Gastritis/patología , Humanos , Ipilimumab/efectos adversos , Inestabilidad de Microsatélites , Necrosis/inducido químicamente , Necrosis/diagnóstico , Necrosis/inmunología , Necrosis/patología , Nivolumab/efectos adversos , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/patología , Activación Viral/inmunologíaRESUMEN
Introduction: Advanced non-small-cell lung cancers with EGFR mutation belong to the models of solid tumors which revealed the concept of oncogene addiction. For that reason, first, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are the major anti-cancer drugs used in this indication. Translational research is currently focused on induced mechanisms of resistance and aims to define the best first therapeutic option and the best multiline strategy.Areas covered: EGFR TKIs, alone or in combination, i.e. anti-angiogenic drugs or chemotherapy, have demonstrated their ability to improve median PFS and OS in large randomized phase 3 trials. All these combinations, now available in first-line for EGFR mutated advanced NSLC, need to integrate multiple factors like patients characteristics (age, co-morbidities, eligibility to platinum-based chemotherapy), presence of brain metastasis at diagnosis, and type of EGFR mutation. This review has 2 aims: (1) to discuss the current knowledge of therapies available in non pre-treated EGFR-mutated NSCLC; (2) to propose the best therapeutic option according to multiple parameters, either clinical or biological.Expert commentary: In 2020, we can affirm that osimertinib the first choice for patients with EGFR-mutated NSCLC. However, this has to be balanced with patient characteristics, type of EGFR mutation and new therapeutic options.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Acrilamidas/administración & dosificación , Acrilamidas/farmacología , Compuestos de Anilina/administración & dosificación , Compuestos de Anilina/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de SupervivenciaRESUMEN
Introduction: Colorectal cancer (CRC) is one of the most frequent and lethal cancers in the world, and therapies are still insufficient. Immune checkpoint inhibitors (ICI) in metastatic CRC (mCRC) have not revolutionized treatment to the extent that they have in melanoma or renal carcinoma. Their use is limited to a molecular niche of mCRC with microsatellite instability (MSI). This review summarizes clinical data published with pembrolizumab in mCRC and also tries to identify potential new strategies.Areas covered: This paper focuses on pembrolizumab in mCRC. We screened all trials on PubMed and ClinicalTrials.gov and describe the most significant ones in our opinion.Expert opinion: Pembrolizumab seems to be effective in tumors with MSI-high status. It defines a new horizon for therapeutic strategy called 'agnostic' medicine. For microsatellite stable (MSS) colorectal cancers, the future challenge will be to successfully redraw the immune microenvironment to make it immunogenic with new therapeutic combinations, including ICI.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Cetuximab/uso terapéutico , Ensayos Clínicos como Asunto , Neoplasias Colorrectales/radioterapia , Quimioterapia Combinada , Humanos , Inmunoterapia , Inestabilidad de Microsatélites , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéuticoRESUMEN
OBJECTIVE: Splanchnic vein thrombosis (SVT) is a potentially severe complication of pancreatitis. The aim of this single-center, retrospective cohort study was to investigate the incidence of SVT and to determine the connected risk factors. METHODS: All consecutive patients with acute pancreatitis (AP) managed in our hospital were included. The primary outcome was the occurrence of SVT and data was collected in accordance with Ranson's criteria. RESULTS: A total of 318 patients were included, of whom 124 (39.0%) were women. Biliary lithiasis was the main cause of pancreatitis (n = 156, 49.1%). A total of 19 (6.0%) SVT were identified. In univariate analysis, alcohol intake, smoking and male gender were associated with SVT (P = 0.005, 0.003 and 0.007, respectively). Biological parameters significantly associated with thrombosis were lactate dehydrogenase (LDH) < 500 U/L and hyperglycemia (≥ 10 mmol/L) (P = 0.009 and 0.016, respectively). In multivariate analysis, prothrombin time >75% was a protective factor against thrombosis (OR 0.148, P = 0.019). Leukocytes >10 × 10(9)/L (OR 6.397, P = 0.034), hyperglycemia (≥ 10 mmol/L) (OR 6.845, P = 0.023), LDH < 500 U/L ((OR 22.61, P = 0.001) and alcoholic etiology (OR 8.960, P = 0.041) were risk factors for SVT. CONCLUSIONS: Alcohol intake, male gender and smoking should focus the physician's attention on the risk of SVT. When further associated with certain biological parameters, the physicians should consider therapeutic anticoagulation to prevent SVT.