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Current US lung cancer screening recommendations limit eligibility to adults with a pack-year (PY) history of ≥20 years and the first 15 years since quit (YSQ). The authors conducted a systematic review to better understand lung cancer incidence, risk and mortality among otherwise eligible individuals in this population beyond 15 YSQ. The PubMed and Scopus databases were searched through February 14, 2023, and relevant articles were searched by hand. Included studies examined the relationship between adults with both a ≥20-PY history and ≥15 YSQ and lung cancer diagnosis, mortality, and screening ineligibility. One investigator abstracted data and a second confirmed. Two investigators independently assessed study quality and certainty of evidence (COE) and resolved discordance through consensus. From 2636 titles, 22 studies in 26 articles were included. Three studies provided low COE of elevated lung cancer incidence beyond 15 YSQ, as compared with people who never smoked, and six studies provided moderate COE that the risk of a lung cancer diagnosis after 15 YSQ declines gradually, but with no clinically significant difference just before and after 15 YSQ. Studies examining lung cancer-related disparities suggest that outcomes after 15 YSQ were similar between African American/Black and White participants; increasing YSQ would expand eligibility for African American/Black individuals, but for a significantly larger proportion of White individuals. The authors observed that the risk of lung cancer not only persists beyond 15 YSQ but that, compared with individuals who never smoked, the risk may remain significantly elevated for 2 or 3 decades. Future research of nationally representative samples with consistent reporting across studies is needed, as are better data from which to examine the effects on health disparities across different populations.
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Neoplasias Pulmonares , Adulto , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Detecção Precoce de Câncer/efeitos adversos , IncidênciaRESUMO
Lung cancer causes the most cancer-related deaths worldwide. In recent years, molecular and immunohistochemical techniques have rapidly developed, further inaugurating an era of personalized medicine for lung cancer. The rare subset of lung cancers accounts for approximately 10%, each displaying distinct clinical characteristics. Treatments for rare lung cancers are mainly based on evidence from common counterparts, which may lead to unsolid clinical benefits considering intertumoral heterogeneity. The increasing knowledge of molecular profiling of rare lung cancers has made targeting genetic alterations and immune checkpoints a powerful strategy. Additionally, cellular therapy has emerged as a promising way to target tumor cells. In this review, we first discuss the current status of targeted therapy and preclinical models for rare lung cancers, as well as provide mutational profiles by integrating the results of existing cohorts. Finally, we point out the challenges and future directions for developing targeted agents for rare lung cancer.
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Antineoplásicos , Neoplasias Pulmonares , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/uso terapêutico , Medicina de Precisão/métodos , Terapia de Alvo MolecularRESUMO
BACKGROUND: Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment. METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool. RESULTS: Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine. CONCLUSIONS: Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.
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Benzimidazóis , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non-invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour-related analytes. The advent of multiomics - enabled by deep learning algorithms - offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi-marker, multi-analyte and multi-source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues.
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Emerging evidence suggests that the prognosis of patients with lung adenocarcinoma can be determined from germline variants and transcript levels in nontumoral lung tissue. Gene expression data from noninvolved lung tissue of 483 lung adenocarcinoma patients were tested for correlation with overall survival using multivariable Cox proportional hazard and multivariate machine learning models. For genes whose transcript levels are associated with survival, we used genotype data from 414 patients to identify germline variants acting as cis-expression quantitative trait loci (eQTLs). Associations of eQTL variant genotypes with gene expression and survival were tested. Levels of four transcripts were inversely associated with survival by Cox analysis (CLCF1, hazard ratio [HR] = 1.53; CNTNAP1, HR = 2.17; DUSP14, HR = 1.78; and MT1F: HR = 1.40). Machine learning analysis identified a signature of transcripts associated with lung adenocarcinoma outcome that was largely overlapping with the transcripts identified by Cox analysis, including the three most significant genes (CLCF1, CNTNAP1, and DUSP14). Pathway analysis indicated that the signature is enriched for ECM components. We identified 32 cis-eQTLs for CNTNAP1, including 6 with an inverse correlation and 26 with a direct correlation between the number of minor alleles and transcript levels. Of these, all but one were prognostic: the six with an inverse correlation were associated with better prognosis (HR < 1) while the others were associated with worse prognosis. Our findings provide supportive evidence that genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Predisposição Genética para Doença , Adenocarcinoma de Pulmão/genética , Pulmão/patologia , Genótipo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The relationship between sleep disturbances and lung cancer is complex and bidirectional. This meta-epidemiological study aimed to explore the potential association between sleep disruption and the risk of pulmonary cancer. METHODS: We conducted a comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve relevant studies. We employed the Newcastle-Ottawa Scale to assess the quality of the observational studies. Stata 17.0 was used to synthesize and conduct a meta-analysis of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We used funnel plot analysis and Egger's regression test to evaluate potential publication bias. RESULTS: A total of 11 studies were included with 469,691 participants. The methodological quality of the included studies ranged from moderate to high. Compared with 7-8 h of sleep time, short sleep duration was associated with a 13% higher lung cancer risk [OR, 1.13; 95%CI: 1.02-1.25; I2 = 67.6%; P = 0.018] and long sleep duration with a 22% higher risk [OR, 1.22; 95%CI: 1.12-1.33; I2 = 6.9%; P < 0.001]. Insomnia symptoms [OR, 1.11; 95%CI: 1.07-1.16; I2 = 0%; P < 0.001] and evening chronotype [OR, 1.15; 95%CI: 1.05-1.26; P = 0.002] were all related to a higher risk of lung cancer. Egger's test revealed no publication bias for sleep duration (P = 0.13). DISCUSSION: This systematic review is the first one which observes positive correction between sleep disturbances and the incidence of lung cancer. While the plausible mechanism is not clear, it is hypothesized that the association of short sleep duration and lung cancer mainly mediated by melatonin secretion and the immune-inflammatory balance. Further studies are needed to examine whether other risk factors, such as age, occupation, cumulative effect of sleep disturbances might mediate the relationship between sleep disturbances and lung cancer risk. CONCLUSION: The present study revealed that insufficient and excessive sleep duration, insomnia symptoms, and evening chronotype were significantly predictive of an increased risk of lung cancer. This finding underscores the need to account for sleep disturbances as an independent risk factor for evaluating susceptibility to lung cancer. TRIAL REGISTRATION: CRD42023405351.
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Neoplasias Pulmonares , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Neoplasias Pulmonares/epidemiologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Sono , Estudos EpidemiológicosRESUMO
OBJECTIVES: To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PET/CT. METHODS: A data set consisting of 364 FDG-PET/CTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PET/CT series. The data set was split into a training (n = 216), validation (n = 74), and internal test data set (n = 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FP/c) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PET/CTs from another institution. RESULTS: Sensitivity for T lesions was 86.2% (95% CI: 77.2-92.7) at a FP/c of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate = 88.8% (95% CI: 82.5-93.5%) and FP/c = 2.7). CONCLUSIONS: Retina U-Nets are a valuable tool for tumor detection tasks on PET/CT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available. KEY POINTS: ⢠Detection of malignant lesions in PET/CT with Retina U-Net is feasible. ⢠All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. ⢠Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging.
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Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Neoplasias Pulmonares/diagnóstico por imagem , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. METHODS: In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. RESULTS: Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. CONCLUSIONS: Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. KEY POINTS: ⢠Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. ⢠Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. ⢠Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Enfisema , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/diagnóstico por imagem , Fumantes , Estudos Longitudinais , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Doença da Artéria Coronariana/diagnóstico por imagemRESUMO
BACKGROUND: Routine concordance evaluation between pathology and imaging findings was introduced for CT-guided biopsies. PURPOSE: To analyze malignancy rate in concordant, discordant, and indeterminate non-malignant results of CT-guided lung biopsies. METHODS: Concordance between pathology results and imaging findings of consecutive patients undergoing CT-guided lung biopsy between 7/1/2016 and 9/30/2021 was assessed during routine meetings by procedural radiologists. Concordant was defined as pathology consistent with imaging findings; discordant was used when pathology could not explain imaging findings; indeterminate when pathology could explain imaging findings but there was concern for malignancy. Recommendations for discordant and indeterminate were provided. All the malignant results were concordant. Pathology of repeated biopsy, surgical sample, or follow-up was considered reference standard. RESULTS: Consecutive 828 CT-guided lung biopsies were performed on 795 patients (median age 70 years, IQR 61-77), 423/828 (51%) women. On pathology, 224/828 (27%) were non-malignant. Among the non-malignant, radiology-pathology concordance determined 138/224 (62%) to be concordant with imaging findings, 54/224 (24%) discordant, and 32/224 (14%) indeterminate. When compared to the reference standard, 33/54 (61%) discordant results, 6/30 (20%) indeterminate, and 3/133 (2%) concordant were malignant. The prevalence of malignancy in the three groups was significantly different (p < 0.001). Time to diagnosis was significantly different between patients who reached the diagnosis with imaging follow-up (median 114 days, IQR 69-206) compared to repeat biopsy (33 days, IQR 18-133) (p = 0.01). CONCLUSION: Routine radiology-pathology concordance evaluation of CT-guided lung biopsy correctly identifies patients at high risk for missed diagnosis of malignancy. Repeat biopsy is the fastest method to reach diagnosis. CLINICAL RELEVANCE STATEMENT: A routine radiology-pathology concordance assessment identifies patients with non-malignant CT-guided lung biopsy result who are at greater risk of missed diagnosis of malignancy. KEY POINTS: ⢠A routine radiology-pathology concordance evaluation of CT-guided lung biopsies classified 224 non-malignant results as concordant, discordant, or indeterminate. ⢠The percentage of malignancy on follow-up was significantly different in concordant (2%), discordant (61%), and indeterminate (20%) (p < 0.001). ⢠Time to definitive diagnosis was significantly shorter with repeat biopsy (33 days), compared to imaging follow-up (114 days), p = 0.01.
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OBJECTIVES: To assess the feasibility of the UTE-MRI radiomic model in predicting the micropapillary and/or solid (MP/S) patterns of surgically resected lung adenocarcinoma. MATERIALS AND METHODS: We prospectively enrolled 74 lesions from 71 patients who underwent UTE-MRI and CT before curative surgery for early lung adenocarcinoma. For conventional radiologic analysis, we analyzed the longest lesion diameter and lesion characteristics at both UTE-MRI and CT. Radiomic features were extracted from the volume of interest of the lesions and Rad-scores were generated using the least absolute shrinkage and selection operator with fivefold cross-validation. Six models were constructed by combining the conventional radiologic model, UTE-MRI Rad-score, and CT Rad-score. The areas under the curves (AUCs) of each model were compared using the DeLong method. Early recurrence after curative surgery was analyzed, and Kaplan-Meier survival analysis was performed. RESULTS: Twenty-four lesions were MP/S-positive, and 50 were MP/S-negative. The longitudinal size showed a small systematic difference between UTE-MRI and CT, with fair intermodality agreement of lesion characteristic (kappa = 0.535). The Rad-scores of the UTE-MRI and CT demonstrated AUCs of 0.84 and 0.841, respectively (p = 0.98). Among the six models, mixed conventional, UTE-MRI, and CT Rad-score model showed the highest diagnostic performance (AUC = 0.879). In the survival analysis, the high- and low-risk groups were successfully divided by the Rad-score in UTE-MRI (p = 0.01) and CT (p < 0.01). CONCLUSION: UTE-MRI radiomic model predicting MP/S positivity is feasible compared with the CT radiomic model. Also, it was associated with early recurrence in the survival analysis. CLINICAL RELEVANCE STATEMENT: A radiomic model utilizing UTE-MRI, which does not present a radiation hazard, was able to successfully predict the histopathologic subtype of lung adenocarcinoma, and it was associated with the patient's recurrence-free survival. KEY POINTS: ⢠No studies have reported the ultrashort echo time (UTE)-MRI-based radiomic model for lung adenocarcinoma. ⢠The UTE-MRI Rad-score showed comparable diagnostic performance with CT Rad-score for predicting micropapillary and/or solid histopathologic pattern. ⢠UTE-MRI is feasible not only for conventional radiologic analysis, but also for radiomics analysis.
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BACKGROUND: Survivors of lung cancer and their partners often have complex unresolved physical, psychosocial, and behavioral needs that can negatively affect the survivors' and partners' well-being. This systematic review aimed to (1) examine the content and delivery of mindfulness-based interventions (MBIs) and (2) summarize and synthesize the current evidence for effectiveness of MBIs targeting survivors of lung cancer and/or one selected partner (dyads). METHOD: Six databases were searched for interventional studies published in English between 1980 and June 2020 using three terms (lung neoplasms, mindfulness, caregivers). For outcome measures, the interventions focused on behavioral change (meditation, yoga, stretching, breathing), symptom management (dyspnea, fatigue, sleep disruption, anxiety, depression, stress reduction), and knowledge. Two reviewers independently assessed article eligibility. One reviewer performed and another independently verified data extraction. The Cochrane risk-of-bias tool for randomized trials was used to critically appraise RCTs. RESULTS: Searching yielded 307 records, of which 64 were assessed for eligibility. Six studies investigated the impact of an MBI on survivors and partners. Four studies were single-arm feasibility studies; two were RCTs. Two feasibility studies and one RCT recruited romantic couples whereas the others recruited asymmetrical dyads. The single-arm studies reported strong feasibility and acceptability. RCTs reported significant outcomes for reduced cancer-related distress and depression, and improved QOL, self-compassion, mindfulness skills, and rumination. CONCLUSION: Dyadic intervention research is a growing field. Few interventions target individuals with lung cancer and their partners. No interventions target partners alone. Future research should evaluate rigorous methodologies that enhance the understanding of independent and interdependent health-related effects within dyads and across relationships and settings.
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Neoplasias Pulmonares , Atenção Plena , Humanos , Qualidade de Vida/psicologia , Atenção Plena/métodos , Neoplasias Pulmonares/terapia , Ansiedade/psicologia , SobreviventesRESUMO
Objective: Few psychosocial interventions have been tailored to meet the unique needs of patients diagnosed with lung cancer. This pilot study developed and tested a six-week intervention for reducing lung cancer stigma.Design and Subjects: Guided by qualitative interviews conducted with 9 lung cancer patients and 5 thoracic oncology care providers, Acceptance and Commitment Therapy was adapted for treatment of lung cancer stigma (ACT-LCS). In a subsequent single arm pilot study, 22 lung cancer patients reporting high levels of stigma completed the intervention.Setting: NCI-designated cancer centers in the Southwestern and Eastern United States.Results: Of 46 eligible patients, 22 provided consent, with 20 completing the intervention (10 in-person, 10 telehealth). Overall stigma decreased across timepoints, largely driven by reductions in internalized stigma. There were also significant reductions in social isolation, sleep disturbance, and fatigue.Conclusions: The ACT-LCS protocol demonstrates preliminary feasibility and acceptability. This intervention may be particularly suited for helping patients navigate feelings associated with internalized stigma.
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Terapia de Aceitação e Compromisso , Neoplasias Pulmonares , Humanos , Estados Unidos , Projetos Piloto , Estudos de Viabilidade , Estigma Social , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/psicologiaRESUMO
Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5-year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro- and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.
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Exossomos , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/metabolismo , Microambiente Tumoral/genéticaRESUMO
Osimertinib is active against T790M-positive epidermal growth factor receptor mutant non-small cell lung cancer. We enrolled 122 sensitive epidermal growth factor receptor mutant non-small cell lung cancer patients who were planned to receive or were receiving first-/second-generation epidermal growth factor receptor tyrosine kinase inhibitors without disease progression and monitored plasma T790M every 1-2 months using the cobas® EGFR Mutation Test v2. We previously reported the concordance between T790M status in plasma and tissue. This is the final report on the sensitivity of plasma T790M and the efficacy of sequential osimertinib. The sensitivity was 21.1% (95% confidence interval: 6.1-45.6%). The best overall response was 25.0% (95% confidence interval: 9.8-46.7) in the plasma T790M-positive group and 28.6% (95% confidence interval: 8.4-58.1) in the plasma T790M-negative but tissue T790M-positive group. Median progression-free survival was 7.9 months (95% confidence interval: 4.7-17.5) for the former and 4.4 months (95% confidence interval: 3.0-N.E.) for the latter, with no statistically significant difference (P = 0.74).
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Opioids have an important role in symptom management for people with advanced cancer. Clinical guidelines recommend patient education to ensure the safe use of opioids; however, no Australian studies have explored current education and safeguarding practices when opioids are initiated to advanced cancer patients. AIMS: To investigate risk assessment, safeguarding and education practices when opioids are first prescribed to advanced lung cancer patients. METHODS: A retrospective medical record audit of outpatients with advanced non-small cell lung cancer seen at a tertiary Australian hospital between 1 January 2015 and 31 December 2019 and prescribed strong opioids for cancer-related symptoms. RESULTS: Of 1022 patients attending the lung cancer clinic, 205 were newly initiated on an opioid. Opioid-related risks including previous recreational drug use (28; 13.6%) and history of falls (16; 7.9%) were infrequently documented. Opioid-related safeguards and adverse effects management were variably instituted: written general practitioner correspondence at opioid initiation (62; 30%), clinic follow up (186; 91%) and laxative co-prescription (55; 26.8%). Most patients (137; 66.8%) received no documented opioid education on drug initiation. There was no association between age (P = 0.653), number of comorbidities (P = 0.569) or chronic alcohol use (P = 0.263) and the provision of education on opioid initiation. Palliative care doctors or nurse practitioners were eight times more likely to document opioid education than medical oncologists (odds ratio = 8.5; confidence interval = 2.9-24.8; P < 0.0001). CONCLUSION: Guideline-recommended risk assessment, safeguards and patient education were infrequently documented when opioids were initiated. Clinician training, decision-assist prompts in electronic prescribing software and written education resources for patients may address these gaps in care.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Laxantes , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Educação de Pacientes como Assunto , Prescrições , Auditoria Clínica , Padrões de Prática MédicaRESUMO
AIMS: The aims of this study were to evaluate the safety, feasibility and outcomes of ambulation within 2 h after thoracoscopic surgery in patients with lung cancer. BACKGROUND: There are no consensus guidelines on the ideal time for early ambulation following thoracic surgery, although enhanced recovery programmes have been proposed since years. METHODS: This non-randomized, concurrent-control study was conducted on patients who underwent thoracoscopic surgery between October 2020 and February 2021. Participants were assigned to either the observation group (ambulation within 2 h of extubation) or the control group (ambulation on the first postoperative day). RESULTS: Of the 325 patients who were eligible, 227 were included in the study. Eighty-three per cent of patients were able to walk any distance within 2 h of extubation, and no adverse events occurred in patients. The length of hospital stay and time to first postoperative flatus were significantly shorter in the observation group than in the control group. There were no differences in the occurrence of postoperative complications and orthostatic hypotension, readmission rate and 6-min walk distance at discharge. CONCLUSION: Ambulation within 2 h of extubation was safe and feasible and could lead to better recovery in patients with lung cancer undergoing thoracoscopic surgery.
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Neoplasias Pulmonares , Estudos de Viabilidade , Humanos , Tempo de Internação , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Toracoscopia , CaminhadaRESUMO
Pleuropulmonary blastoma (PPB) is a rare malignant lung tumor in the pediatric population and occurs mainly in young children. Its clinical presentation is usually nonspecific. We report a rare occurrence of this tumor in a 15-year-old girl, who presented with symptoms mimicking respiratory tract infection and was nonresponsive to the initial treatment. Imaging investigations revealed a large solid lesion in the left hemithorax with a mass effect on the adjacent structures. Biopsy demonstrated primitive cells with blastematous appearances, and the stroma cells were positive for vimentin and desmin, consistent with PPB. Unfortunately, she died from neutropenic sepsis while undergoing chemotherapy. This report highlights the epidemiology of PPB, its imaging and histopathological features, overview of prognosis, and clinical management.
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OBJECTIVE: Multiple cohort studies have compared surgical resection with CT-guided percutaneous ablation for patients with stage 1 non-small cell lung cancer (NSCLC); however, the results have been heterogeneous. This systematic review and meta-analysis aims to compare surgery with ablation for stage 1 NSCLC. METHOD: A search of five databases was performed from inception to 5 July 2020. Studies were included if overall survival (OS), cancer-specific survival (CSS), and/or disease-free survival (DFS) were compared between patients treated with surgical resection versus ablation (radiofrequency ablation (RFA) or microwave ablation (MWA)) for stage 1 NSCLC. Pooled odds ratios (OR) were calculated. RESULTS: A total of eight studies were included (total 792 patients: 460 resection and 332 ablation). There were no significant differences in 1- to 5-year OS or CSS between surgery versus ablation. There were significantly better 1- and 2-year DFS for surgery over ablation (OR 2.22, 95% CI 1.14-4.34; OR 2.60, 95% CI 1.21-5.57 respectively), but not 3- to 5-year DFS. Subgroup analysis demonstrated no significant OS difference between lobectomy and MWA, but there were significantly better 1- and 2-year OS with sublobar resection (wedge resection or segmentectomy) versus RFA (OR 2.85, 95% CI 1.33-6.10; OR 4.54, 95% CI 2.51-8.21, respectively). In the two studies which only included patients with stage 1A NSCLC, pooled outcomes demonstrated no significant differences in 1- to 3-year OS or DFS between surgery versus ablation. CONCLUSION: Surgical resection of stage 1 NSCLC remains the optimal choice. However, for non-surgical patients with stage 1A, ablation offers promising DFS, CSS, and OS. Future prospective randomized controlled trials are warranted. KEY POINTS: ⢠Surgical resection of stage 1 NSCLC remains the optimal choice. ⢠In patients with stage 1A NSCLC who are not surgical candidates, CT-guided microwave or radiofrequency ablation may be an alternative which offers promising disease-free survival and overall survival.
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Carcinoma Pulmonar de Células não Pequenas , Ablação por Cateter , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Tomografia Computadorizada por Raios XRESUMO
Rationale: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial.Objectives: To define the relationship between pleural plaques and lung cancer risk.Methods: Subjects were from two cohorts: 1) crocidolite mine and mill workers and Wittenoom Township residents and 2) a mixed-asbestos-fiber, mixed-occupation group. All subjects underwent annual review since 1990, chest X-ray or low-dose computed tomography scan, and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios (HRs) for lung cancer incidence by sex, tobacco smoking, asbestos exposure, presence of asbestosis, and pleural plaques.Measurements and Main Results: For all 4,240 subjects, mean age at follow up was 65.4 years, 3,486 (82.0%) were male, 1,315 (31.0%) had pleural plaques, and 1,353 (32.0%) had radiographic asbestosis. Overall, 3,042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. In total, 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos, and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR, 1.03; 95% confidence interval, 0.64-1.67; P = 0.89; cohort 2: HR, 0.75; 95% confidence interval, 0.45-1.25; P = 0.28).Conclusions: The presence of pleural plaques on radiologic imaging does not confer additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.
Assuntos
Amianto/efeitos adversos , Asbestose/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Exposição Ocupacional/efeitos adversos , Doenças Pleurais/fisiopatologia , Adulto , Asbestose/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/epidemiologia , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
BACKGROUND: Early involvement of palliative care and advance care planning improves quality-of-life outcomes and survival for patients with advanced lung cancer; however, there are barriers to implementation. AIMS: A single-centre prospective audit reviewing 'Goals of Care' (GOC) form completion and palliative care referrals in an oncology clinic was undertaken with the aim of increasing GOC completion and palliative care referrals for patients with advanced lung cancer. METHODS: Involved physicians attended a communication skills course and then received a communication-priming intervention. Clinicopathological factors associated with GOC completion and palliative care referral were explored. RESULTS: A total of 84 patients receiving palliative treatment for advanced lung cancer was enrolled. Clinicopathological factors, such as poorer performance status, were associated with higher likelihood of GOC completion (P = 0.018) prior to the intervention. Male sex (P = 0.023), absence of sensitising epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement (P = 0.017), type of systemic therapy (P = 0.031) and poorer performance status (P < 0.001) were associated with higher likelihood of palliative care referral. The intervention improved GOC completion (relative risk (RR) 1.29, P = 0.004); however, this was not sustained in a follow-up audit (RR 0.98, P = 0.92) and there was no change in palliative care referral rate (RR 2.5, P = 0.16). Predictors of palliative referral following clinical review included age (RR 1.16, P = 0.001), male sex (RR 14.2, P = 0.02) and poorer performance status (RR 1.76, P < 0.001). CONCLUSIONS: Communication-priming interventions can improve GOC completion for patients with advanced lung cancer. Further investigation is needed to pursue sustainable options for managing this complex patient group and improve guideline-adherence and patient care.