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BACKGROUND: Survivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life. METHODS: Adults hospitalised for severe-to-critical COVID-19 were evaluated at 3â months and up to 12â months post-hospital discharge in this prospective, multicentre, cohort study. RESULTS: Among 485 enrolled participants, 293 (60%) were reassessed at 6â months and 163 (35%) at 12â months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12â months, respectively. At 3â months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (D LCO) and significant radiological sequelae, respectively. During extended follow-up, both D LCO and forced vital capacity percentage predicted increased by means of +4 points at 6â months and +6 points at 12â months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with D LCO at 3â months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images. CONCLUSIONS: Although pulmonary function and radiological abnormalities improved up to 1â year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Estudios de Cohortes , Estudios Prospectivos , Calidad de Vida , Pulmón/diagnóstico por imagen , Oxígeno/uso terapéuticoRESUMEN
Recently, developments of therapies that target abnormally activated signaling pathways are increasing for patients with non-small cell lung cancer. EGFR mutations are found in about 10% of lung cancers, especially in adenocarcinoma, women and non-smokers. Three EGFR inhibitors (erlotinib, gefitinib and afatinib) received a European marketing authorization for up to first line treatment of EGFR mutated NSCLC. Effectiveness of EGFR inhibitors is higher than conventional chemotherapy. Third generation EGFR inhibitors (rociletinib, AZD9291) are effective for patients who develop a resistance mutation such as T790M resistance mutation; they obtained temporary authorization for use in France in 2015. The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line. Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib. INCA supports ACSé program evaluating the efficacy of crizotinib in NSCLC amplified for MET or translocated for ROS1 and ACSé program evaluating the efficacy of vemurafenib in tumors non melanoma mutated V600E BRAF. The role of other biomarkers such as KRAS, BRAF, HER2 and PI3KCA mutations remains to be defined in NSCLC.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Molecular Dirigida , Proteínas de Neoplasias/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Ensayos Clínicos como Asunto , Femenino , Genes Relacionados con las Neoplasias , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Masculino , Mutación , Proteínas de Neoplasias/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: Only a small proportion of patients with advanced non-small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The aim of this study was to identify the factors associated with long-term survival of patients with advanced NSCLC. METHODS: Patients who had received chemotherapy for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied retrospectively. Data were gathered prospectively from a comprehensive database. Long-term survivors (>2 years) were compared with the other patients, with respect to clinical, biological and tumour-node-metastasis criteria. RESULTS: Data for 245 consecutive patients were collected. Thirty nine patients (15.9%) survived for more than 2 years. Long-term survivors were more likely to have had metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01), a performance status (PS) of 0-1 at first progression of the tumour (P = 0.002), a tumour that was controlled with first (P < 0.0001) and second-line (P = 0.004) chemotherapy, maintenance therapy (P = 0.001), curative surgery (P < 0.0001), time to first progression of the tumour of >3 months (P < 0.0001), normal LDH levels at diagnosis (P = 0.049), and a haemoglobin concentration >110 g/L at first progression of the tumour (P = 0.02). In multivariate analysis, surgery, maintenance treatment, time to first progression of the tumour of >3 months, a PS of 0-1 at first progression, the number of chemotherapy agents received, and LDH levels, were significant predictors of long-term survival. CONCLUSIONS: Assessment of these factors, and the use of maintenance therapy, when possible, may identify a population of patients with NSCLC that is likely to have a prolonged life expectancy.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Quimioterapia de Mantención , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Femenino , Humanos , Esperanza de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The setting up of an advanced practice nursing activity to monitor patients with severe or very severe pneumonia associated with Severe Acute Respiratory Syndrome Coronavirus 2, is a reponse to the population's new health care needs and a massive influx of patients. The skills of the advanced practice nurse are mobilised in this context in order to carry out prevention missions and screening for potential sequelae which could lead to chronic respiratory failure.
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Enfermería de Práctica Avanzada , COVID-19 , Neumonía Viral , COVID-19/complicaciones , Humanos , Neumonía Viral/enfermería , Neumonía Viral/virología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. METHODS: We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. RESULTS: Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. CONCLUSION: We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.
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Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/genética , Antígeno B7-H1/genética , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
OBJECTIVE: To describe the efficacy and safety of biologics for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: A retrospective European collaborative study was conducted in patients with EGPA who received treatment with biologics for refractory and/or relapsing disease. RESULTS: Among the 147 patients with EGPA included in the study, 63 received rituximab (RTX), 51 received mepolizumab (MEPO), and 33 received omalizumab (OMA). At the time of inclusion, the median Birmingham Vasculitis Activity Score (BVAS) was 8.5 (interquartile range [IQR] 5-13) in the RTX group, while the median BVAS in the OMA group was 2 (IQR 1-4.5) and the median BVAS in the MEPO group was 2 (IQR 1-5). In patients receiving RTX, the median BVAS declined both at 6 months (median 1, IQR 0-4.5) and at 12 months (median 0, IQR 0-2), and the frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 49%, 24%, 24%, and 3%, respectively. For the treatment of glucocorticoid (GC)-dependent asthma, patients who received MEPO had a much better GC-sparing effect and overall response than did patients who received OMA. The frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 15%, 33%, 48%, and 4%, respectively, in the OMA group and 78%, 10%, 8%, and 4%, respectively, in the MEPO group. Remission rates at 12 months were 76% and 82% among patients receiving MEPO at a doses of 100 mg and 300 mg, respectively. CONCLUSION: These results suggest that RTX could be effective in treating relapses of EGPA vasculitis. MEPO is highly effective with a good safety profile in patients with GC-dependent asthma. Our data suggest that 100 mg MEPO monthly could be an acceptable dosage for first-line therapy in selected instances of EGPA, recognizing, however, that this has not been compared to the validated dosage of 300 mg monthly.
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Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/fisiopatología , Síndrome de Churg-Strauss/fisiopatología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Omalizumab/uso terapéutico , Recurrencia , Estudios Retrospectivos , Rituximab/uso terapéutico , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Risk factors and prevention of lung cancer. In France, lung cancer is the leading cause of death from cancer with more than 30,000 deaths per year. The vast majority (85%) of lung cancer are due to tobacco and the duration of smoking has a greater impact than the amount smoked. Passive smoking increases the risk of lung cancer and is responsible for around 25% of lung cancers in non-smokers in France. The risk of lung cancer linked to cannabis smoke hasn't been demonstrated, but is suspected. Other carcinogens found in certain workplaces, such as asbestos, or in the environment, such as radon in granite soils and urban air pollution, increase the risk of lung cancer. The maximum benefit on lung cancer mortality reduction should be obtained by combining smoking cessation and lung cancer screening by chest CT. Lung cancer screening has shown its effectiveness, but is currently not recommended in France. Measures to promote smoking cessation are known and include public health measures to de-normalize tobacco (neutral packaging, ban on advertising, significant increase in its price) and treatments that have been shown to be effective in smoking cessation: nicotine replacement therapy, varenicline and cognitive behavioral therapy.
Facteurs de risque et prévention des cancers du poumon. En France, le cancer du poumon est la première cause de mortalité par cancer, avec plus de 30 000 décès par an. La très grande majorité (85 %) des cancers du poumon sont dus au tabac. La durée du tabagisme a un impact plus important que la quantité fumée. Le tabagisme passif augmente aussi le risque de cancer du poumon et serait responsable d'environ 25 % des cancers du non-fumeur en France. Le risque de cancer du poumon lié à la fumée de cannabis n'est à ce jour pas démontré mais est suspecté. D'autres cancérogènes trouvés dans certains lieux de travail, tels que l'amiante, ou dans l'environnement, tel que le radon des sols granitiques, et la pollution de l'air des villes peuvent augmenter le risque de cancer du poumon. Le bénéfice maximal sur la réduction de la mortalité par cancer du poumon pourrait être observé par le sevrage tabagique et le dépistage par scanner thoracique. Le dépistage a montré son efficacité, mais n'est pas à ce jour recommandé en France. Les mesures pour favoriser le sevrage tabagique comportent les mesures de santé publique pour dénormaliser le tabac (paquet neutre, interdiction de la publicité, augmentation importante de son prix) et les traitements qui ont démontré leur efficacité dans le sevrage tabagique : la substitution nicotinique, la varénicline et les thérapies cognitives et comportementales.
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Neoplasias Pulmonares , Cese del Hábito de Fumar , Detección Precoz del Cáncer , Francia/epidemiología , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/prevención & control , Factores de Riesgo , Dispositivos para Dejar de Fumar TabacoRESUMEN
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. METHODS: All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. RESULTS: Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). CONCLUSIONS: Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.
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Carcinoma , Neoplasias Pulmonares , Antígeno B7-H1/uso terapéutico , Humanos , Inhibidores de Puntos de Control Inmunológico , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
INTRODUCTION: KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC. METHODS: In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype. RESULTS: Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5-9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2-5.1) for first-line treatment and 4.8 months (95% CI: 4.3-6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations. CONCLUSIONS: KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
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The combination of surgery with chemotherapy is the standard of care in stage II-IIIa surgical non small cell lung cancer. The survival benefit of chemotherapy corresponds to 4 to 8%. This benefit has been proved mainly by postoperative chemotherapy trials. When the positive results were published, most preoperative chemotherapy trials were closed. Nevertheless, the same survival benefit could be expected in preoperative chemotherapy trials. Furthermore preoperative chemotherapy has advantages: compliance of chemotherapy is excellent and tumor chemosensibility can be estimated. As the sequence of chemotherapy and surgery is not yet established, the French recommendations of the SOR (Standards, Options and Recommendations) suggest either pre or postoperative chemotherapy.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Terapia Neoadyuvante , HumanosRESUMEN
BACKGROUND: Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety. METHODS: Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge. RESULTS: Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P=0.04), mostly women (61% vs. 30%, P=0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P=0.03), a better general state of health (100% performance status 0-1 vs. 74%, P=0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P=0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P=0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P=0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients. CONCLUSION: Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/mortalidad , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Ex-Fumadores , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Supervivencia sin Progresión , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Retratamiento/métodos , Retratamiento/estadística & datos numéricos , FumadoresRESUMEN
Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.
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Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neumonía/inducido químicamente , Corticoesteroides/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Diagnóstico Precoz , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Neumonía/epidemiología , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Calpain 1 is a proinflammatory calcium-activated cysteine protease, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the externalization of calpain 1 and the release of soluble TLR2 during tumor progression of pulmonary lepidic predominant adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n=68). Source of calpain was analyzed by immunohistochemistry and soluble TLR2 by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (P=0.003). TLR2 was expressed on PMN and tumor cells and decreased after calpain exposure. Soluble fragment of TLR2 in BALF supernatants was correlated to the extracellular calpain 1 concentration (r=0.624; P<0.001), and its high level was associated with tumor progression and a pro-inflammatory environment. Extracellular calpain 1 secreted by tumor cells, could participate in inflammatory microenvironment and tumor progression through TLR2 in LPA.
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Adenocarcinoma/metabolismo , Líquido del Lavado Bronquioalveolar/química , Calpaína/análisis , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor Toll-Like 2/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Calpaína/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Inflamación/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Proteínas de Neoplasias/análisis , Neutrófilos/metabolismo , PronósticoRESUMEN
INTRODUCTION: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. METHODS: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. RESULTS: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. CONCLUSION: IHC is not a relevant screening tool for MET abnormalities in LSC.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Exones/genética , Amplificación de Genes , Neoplasias Pulmonares/diagnóstico , Mutación , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Gigantes/diagnóstico , Carcinoma de Células Gigantes/genética , Carcinoma de Células Gigantes/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/metabolismoRESUMEN
Platinum-based perioperative chemotherapy is actually the standard of care in stage II-IIIa non-small cell lung cancer (NSCLC). A benefit may also be seen in stage IB NSCLC with tumors of more than 4cm of diameter. Perioperative chemotherapy improves 5-year survival of 4 to 15%. This benefit is mainly proved by postoperative chemotherapy trials. Nevertheless, preoperative chemotherapy has advantages: a better tolerance, an estimation of tumor chemosensibility, without an increased postoperative morbimortality. However, pTNM and pathological tumor analyses are modified. Indications of postoperative radiotherapy are limited. In early stage NSCLC (stage I-II), radiotherapy worsens survival. Radiotherapy is routinely achieved in NSCLC with parietal tumor invasion and incomplete tumor resection. Indications of immunotherapy and targeted therapies in case of oncogenic addiction remain to be established in resected NSCLC. Several biomarkers are studied to better describe the indications of perioperative chemotherapy: recognize groups of patients with a worse prognosis and distinguish chemosensibility of the tumor.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Factores de Edad , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , Humanos , Inmunoterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Cumplimiento de la Medicación , Terapia Molecular Dirigida , Terapia Neoadyuvante , Compuestos de Platino/uso terapéutico , Radioterapia Adyuvante/efectos adversos , Carga TumoralRESUMEN
Smoking is a public health problem of particular importance during the perioperative period, since it exposes patients scheduled for surgery to risk increases of 20% in hospital mortality and 40% in major postoperative complications. In addition, current smoking increases almost all specific surgical complications. The perioperative period offers a genuine opportunity for smoking cessation. The rate of preoperative smoking cessation can be increased significantly by offering behavior management and the prescription of a nicotine substitute before any scheduled surgical intervention. Preoperative smoking cessation should be routinely recommended independently of the timing of the intervention, even though the benefits increase in proportion with the length of cessation. All professionals of the care pathway (general practitioners, surgeons, anesthetists-intensivists, caregivers) must inform smokers of the positive effects of smoking cessation and offer them dedicated management and personalized follow-up. In children, cessation of parental smoking or removal of the child from environmental tobacco smoke as long before surgery as possible is indispensable.
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Atención Perioperativa/métodos , Periodo Perioperatorio , Fumar , Terapia Conductista , Sistemas Electrónicos de Liberación de Nicotina , Guías como Asunto , Humanos , Nicotina/uso terapéutico , Agonistas Nicotínicos/uso terapéutico , Derivación y Consulta , Cese del Hábito de Fumar , Fumar TabacoRESUMEN
OBJECTIVE: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
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Azatioprina/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Poliangitis Microscópica/tratamiento farmacológico , Poliarteritis Nudosa/tratamiento farmacológico , Adulto , Anciano , Asma/inducido químicamente , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Rinitis/inducido químicamente , Sinusitis/inducido químicamenteRESUMEN
INTRODUCTION: Chemoresistance is a major challenge in the treatment of advanced non-small-cell lung cancer (NSCLC). Because the Sonic hedgehog (Shh) pathway is reactivated in NSCLC, we investigated an association between chemoresistance and Shh activation. PATIENTS AND METHODS: From a cohort of 178 patients with advanced NSCLC treated with platinum-based chemotherapy as first-line treatment, we selected all surgical tumor samples at diagnosis (n = 36). Shh activation was evaluated through Gli1 and Gli2 expression using immunohistochemistry (quantitative score). In vitro treatment studies with cisplatin or vismodegib (Shh pathway inhibitor), or both, were performed on NSCLC cell lines (H322 and A549) and primary cultures from patients with sarcomatoid carcinoma (n = 4). RESULTS: Of the 36 patients, 12 had NSCLC refractory to chemotherapy (R-patients, 33.3%) and 24 had controlled disease (C-patients). Gli1 expression did not differ between the R- and C-patients (P = .35). Gli2 expression was more often positive in the R-patients (41.7% vs. 8.3%; P = .02). Progression-free survival (PFS) and overall survival (OS) in patients with a Gli2-positive score was 2.1 and 8.0 months, respectively, compared with 6.7 and 18.0 months for patients with a Gli2-negative score (P = .03 and P = .002, respectively). On multivariate analysis, the Gli2 score correlated independently with PFS (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.05-6.63; P = .04) and OS (HR, 4.36; 95% CI, 1.67-11.36; P = .003). The sarcomatoid carcinoma cell lines were more resistant to cisplatin than were the H838 and A549 cell lines. The cisplatin-vismodegib combination displayed a synergistic cytotoxic effect in the most chemoresistant cells in vitro. CONCLUSION: The Shh pathway is associated with resistance to platinum-based chemotherapy in NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteínas Hedgehog/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteínas Nucleares/metabolismo , Compuestos de Platino/uso terapéutico , Adulto , Anilidas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Línea Celular Tumoral , Estudios de Cohortes , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Piridinas/farmacología , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Activación Transcripcional/efectos de los fármacos , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína Gli2 con Dedos de ZincRESUMEN
Non-small-cell lung cancer (NSCLC) is the most common non-acquired immune deficiency syndrome-related malignancy responsible for death. Mutational status is crucial for choosing treatment of advanced NSCLC, yet no data is available on the frequency of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations and their impact on NSCLC in human immunodeficiency virus (HIV)-infected patients (HIV-NSCLC). All consecutive HIV-NSCLC patients diagnosed between June 1996 and August 2013 at two Paris university hospitals were reviewed, with tumor samples analyzed for EGFR and KRAS mutational status. Overall, 63 tumor samples were analyzed out of 73 HIV-NSCLC cases, with 63% of advanced NSCLC. There were 60 non-squamous and nine squamous cell carcinomas, with EGFR and KRAS mutations identified in two (3.3%) and seven (11.5%) tumors, respectively. The proportion of KRAS mutations was 29% if solely the more sensitive molecular techniques were considered. The two patients with advanced adenocarcinoma harboring EGFR mutations exhibited lasting partial response to EGFR-tyrosine kinase inhibitors. Overall survival for patients with advanced NSCLC were >30 months for those with EGFR mutations, <3 months for KRAS mutations (n=2), and the median was 9 months [4.1-14.3] for wild-type (n=34). In multivariate analysis, KRAS mutation and CD4<200 cells/µL were associated with poor prognosis (hazard ratio (HR): 24 [4.1-140.2], p=0.0004; HR: 3.1 [1.3-7.5], p=0.01, respectively). EGFR mutation must be investigated in HIV-NSCLC cases due to its predictive and prognostic impact, whereas KRAS mutation is of poor prognostic value. Clinicians should search for drugs dedicated to this target population.