Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 98
Filter
1.
BMC Cancer ; 22(1): 475, 2022 Apr 30.
Article in English | MEDLINE | ID: covidwho-1951119

ABSTRACT

BACKGROUND: Social media platforms are increasingly being used by stakeholders to generate, access, and share health-related information and experiences. Lung cancer is the most common cancer, impacting > 2 million patients globally. This observational study utilized a social listening approach to analyze social media trends and gain insights into stakeholder perceptions of lung cancer. METHODS: This social media study retrospectively collated data from open access blogs, forums, and social networking sites. Social media posts were collected between June 2019-May 2020 from 14 European countries. Using social media aggregator tools, posts comprising lung cancer and non-small cell lung cancer-specific terms were extracted. Manual and automated relevancy algorithms filtered the extracted information to provide the relevant dataset. This contextualized dataset was further mined to generate the final data for analysis. RESULTS: Of 1360 conversations analyzed, 42% were generated by patients/caregivers and 14% by healthcare professionals (HCPs). A majority of patients were 51-70 years old (approximately 50%) and 91% (n = 500/550) had late-stage cancer. Treatment (35%) and disease awareness (30%) were among the most discussed topic of the patient journey. Although the overall treatment sentiment was neutral, chemotherapy was the treatment type with the highest associated negative sentiment (28%); fewer negative sentiments were associated with immunotherapy (9%) and targeted therapy (2%), due to perceptions of longer survival outcomes and fewer side effects. In conversations that discussed clinical endpoints, "survivability" and "overall survival" (47 and 30%, respectively; n = 539) were most frequently mentioned by stakeholders. HCPs mostly used technical terms, whereas patients and caregivers used colloquial terms such as "getting rid of cancer". Emotional wellness was identified to have a huge impact on quality of life in lung cancer. Delay or treatment cancellations due to COVID-19, lack of effective treatments and funding, and lack of empathy by physicians emerged as the key unmet needs among patients/caregivers. CONCLUSIONS: Social listening proved to be an effective tool to explore stakeholders' perceptions and their key unmet needs, typically not available in published literature or databases, and provides HCPs with valuable insights into the distress, doubts, and needs of lung cancer patients and caregivers.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Social Media , Aged , Carcinoma, Non-Small-Cell Lung/therapy , Humans , Lung Neoplasms/therapy , Middle Aged , Quality of Life , Retrospective Studies
2.
Comput Math Methods Med ; 2022: 9422902, 2022.
Article in English | MEDLINE | ID: covidwho-1950460

ABSTRACT

Objective: Molecular targeted drug therapy and chemotherapy are the main treatments for advanced non-small-cell lung cancer, and the combination of both has advantages in prolonging patients' progression-free survival and overall survival. This study investigated the effects of bevacizumab combined with chemotherapy under nursing intervention on CT, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and gastrin-releasing peptide precursor (ProGRP) and prognosis of lung cancer patients. Methods: 102 patients with non-small-cell lung cancer admitted to our hospital from January 2018 to May 2019 were divided into observation group and control group, with 51 cases each. The control group was treated with basic chemotherapy, and the observation group was treated with bevacizumab in combination with the control group, and both groups used nursing interventions. The clinical effects, CYFRA21-1 and ProGRP levels, baseline data, CT parameters, 24-month cumulative survival, and the effects of CYFRA21-1 and ProGRP on long-term survival and lung function were compared. Results: The disease control rate of the observation group was 94.12%, which was significantly higher than that of the control group (76.47%); after 7 d, 30 d, 60 d, and 90 d of treatment, the levels of CYFRA21-1 and ProGRP were statistically downregulated. The difference in lymph node metastasis, lesion diameter, plain Eff-Z, venous stage, and arterial stage normalized iodine concentrations (NIC) was statistically significant; the survival rate at 24 months in the observation group was 74.51% (38/51); the cumulative survival rate at 24 months in the control group was 52.94% (27/51), and the difference was statistically significant (X 2 = 4.980, P = 0.026). The cumulative survival rate at 24 months was significantly lower in patients with high expression of CYFRA21-1 and ProGRP compared with those with low expression of CYFRA21-1 and ProGRP. After treatment, in the observation group, the forceful spirometry (FVC), forceful expiratory volume in one second (FEV1), and FEV1/FVC levels were significantly different from those before treatment and were significantly different from those in the control group. Conclusion: Bevacizumab in combination with standard chemotherapy regimens with nursing interventions could benefit patients with advanced non-small-cell lung cancer and had a good prospect of application.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antigens, Neoplasm , Bevacizumab/therapeutic use , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Keratin-19 , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Peptide Fragments , Prognosis , Protein Precursors , Recombinant Proteins , Tomography, X-Ray Computed
3.
Br J Cancer ; 127(3): 558-568, 2022 08.
Article in English | MEDLINE | ID: covidwho-1947301

ABSTRACT

BACKGROUND: COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales. METHODS: Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR). RESULTS: Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020). CONCLUSION: Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.


Subject(s)
Breast Neoplasms , COVID-19 , Carcinoma, Non-Small-Cell Lung , Colorectal Neoplasms , Lung Neoplasms , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , COVID-19/epidemiology , COVID-19 Testing , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/epidemiology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Delivery of Health Care , Female , Humans , Incidence , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Pandemics , SARS-CoV-2 , Wales/epidemiology
4.
Lung Cancer ; 170: 185-193, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1914798

ABSTRACT

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Small Cell Lung Carcinoma , COVID-19/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung/pathology , Lung Neoplasms/pathology , Pandemics , Radiosurgery/adverse effects
5.
PLoS One ; 17(6): e0270118, 2022.
Article in English | MEDLINE | ID: covidwho-1910670

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of durvalumab compared with Best supportive care (BSC) after chemoradiotherapy in patients with stage III non-small cell lung cancer from healthcare system perspective in China. METHODS: A dynamic state transition model was adopted to simulate life time, direct medical costs and QALYs. In the base case scenario, for patients with unresectable, stage Ⅲ non-small cell lung cancer whose disease has not progressed after platinum-based chemoradiation therapy, the treatment group would use durvalumab whereas the control group would use BSC. Clinical data and health utility were derived from the patient-level data of Asian ethnicity in the PACIFIC trial. Cost of drug acquisition, follow-up, medical service, inspection, terminal care and adverse event treatment were considered in this model. The cost of durvalumab was calculated based on retail prices and Patient Assistance Program. RESULTS: In the base case, the durvalumab group yielded an additional 2.60 LYs and 2.37QALYs (discounted), causing an additional cost of 0.459 million RMB and 0.109 million RMB without and with PAP, so the ICER was 193,898 RMB/QALY and 46,093.12 RMB/QALY respectively. CONCLUSIONS: This study demonstrated that durvalumab can improve the survival of patients with unresectable, stage Ⅲ non-small cell lung cancer whose disease has not progressed after platinum-based chemoradiation therapy and would be a cost-effective option compared with BSC at a willingness to pay (WTP) threshold of 212676 RMB (three times GDP per capita of China in 2019).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal/therapeutic use , China , Cost-Benefit Analysis , Humans , Quality-Adjusted Life Years
6.
J Biopharm Stat ; 32(1): 204-218, 2022 01 02.
Article in English | MEDLINE | ID: covidwho-1873726

ABSTRACT

Randomized controlled trials (RCTs) are the gold standard for evaluation of new medical products. However, RCTs may not always be ethical or feasible. In cases where the investigational product is available outside the trial (e.g., through accelerated approval), patients may fail to enroll in clinical trials or drop out early to take the investigational product. These challenges to enrolling or maintaining a concurrent control arm may compromise timely recruitment, retention, or compliance. This can threaten the study's integrity, including the validity of results. External control arms (ECAs) may be a promising augmentation to RCTs when encountered with challenges that threaten the feasibility and reliability of a randomized controlled clinical trial. Here, we propose the use of ECAs created from patient-level data from previously conducted clinical trials or real-world data in the same indication. Propensity score methods are used to balance observed disease characteristics and demographics in the previous clinical trial or real-world data with those of present-day trial participants assigned to receive the investigational product. These methods are explored in a case study in non-small cell lung cancer (NSCLC) derived from multiple previously conducted open label or blinded phase 2 and 3 multinational clinical trials initiated between 2004 and 2013. The case study indicated that when balanced for baseline characteristics, the overall survival estimates from the ECA were very similar to those of the target randomized control, based on Kaplan-Meier curves and hazard ratio and confidence interval estimates. This suggests that in the future, a randomized control may be able to be augmented by an ECA without compromising the understanding of the treatment effect, assuming sufficient knowledge, measurement, and availability of all or most of the important prognostic variables.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , SARS-CoV-2 , Treatment Outcome
7.
Med Image Anal ; 80: 102491, 2022 08.
Article in English | MEDLINE | ID: covidwho-1867483

ABSTRACT

Segmentation of lung pathology in Computed Tomography (CT) images is of great importance for lung disease screening. However, the presence of different types of lung pathologies with a wide range of heterogeneities in size, shape, location, and texture, on one side, and their visual similarity with respect to surrounding tissues, on the other side, make it challenging to perform reliable automatic lesion segmentation. To leverage segmentation performance, we propose a deep learning framework comprising a Normal Appearance Autoencoder (NAA) model to learn the distribution of healthy lung regions and reconstruct pathology-free images from the corresponding pathological inputs by replacing the pathological regions with the characteristics of healthy tissues. Detected regions that represent prior information regarding the shape and location of pathologies are then integrated into a segmentation network to guide the attention of the model into more meaningful delineations. The proposed pipeline was tested on three types of lung pathologies, including pulmonary nodules, Non-Small Cell Lung Cancer (NSCLC), and Covid-19 lesion on five comprehensive datasets. The results show the superiority of the proposed prior model, which outperformed the baseline segmentation models in all the cases with significant margins. On average, adding the prior model improved the Dice coefficient for the segmentation of lung nodules by 0.038, NSCLCs by 0.101, and Covid-19 lesions by 0.041. We conclude that the proposed NAA model produces reliable prior knowledge regarding the lung pathologies, and integrating such knowledge into a prior segmentation network leads to more accurate delineations.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , COVID-19/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed
8.
Zhongguo Fei Ai Za Zhi ; 25(5): 295-302, 2022 May 20.
Article in Chinese | MEDLINE | ID: covidwho-1847419

ABSTRACT

Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021.
.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Quality of Life
9.
Asian J Surg ; 45(8): 1553-1558, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1814136

ABSTRACT

OBJECTIVE: There is limited literature on patients with a history of COVID-19 pneumonia who underwent anatomical lung resection for non-small cell lung cancer (NSCLC). This study was aimed to share the early postoperative outcomes in patients who underwent lung resection after COVID-19 pneumonia. MATERIALS AND METHODS: We retrospectively evaluated 30 patients who underwent lobectomy with thoracotomy and systematic mediastinal lymph node dissection due to NSCLC in a single center between November 2018 and September 2021. The patients were divided into two groups regarding COVID-19 pneumonia history; the COVID-19 group consisted of 14 patients (46.7%) and the non-COVID-19 group 16 (53.3%) patients. The patients' age, gender, comorbidity, Charlson Comorbidity Index (CCI) score, forced expiratory volume in 1 s (FEV1) value, tumor type and size, resection type, postoperative air leak duration, total drainage volume, drain removal time, postoperative complications, and length of stay (LOS) were recorded. RESULTS: 9 (30%) patients were female, and 21 (70%) were male. The mean age was 62.1 ± 8.91 years. Our comparison of postoperative air leak duration, total drainage volume, time to drain removal, postoperative complications, and LOS between the COVID-19 and non-COVID-19 groups revealed no statistically significant difference. CONCLUSION: Anatomical lung resection can be performed safely in NSCLC patients with a history of COVID-19 pneumonia without significant difference in early postoperative morbidity and mortality.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , COVID-19/complications , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung/pathology , Lung Neoplasms/complications , Lung Neoplasms/surgery , Male , Middle Aged , Pneumonectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects
11.
Expert Rev Anticancer Ther ; 22(5): 549-559, 2022 May.
Article in English | MEDLINE | ID: covidwho-1806096

ABSTRACT

INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement, or both. Multidisciplinary evaluation is essential to discuss multiple treatment options, to outline optimal management, and to examine the main debated topics and critical issues not addressed by current trials and guidelines that influence daily clinical practice. AREAS COVERED: From March to 5 May 2021 ,meetings were scheduled in a webinar format titled 'Radio Talk' due to the COVID-19 pandemic; the faculty was composed of 6 radiation oncologists from 6 different Institutions of Italy, all of them were the referring radiation oncologist for lung cancer treatment at their respective departments and were or had been members of AIRO (Italian Association of Radiation Oncology) Thoracic Oncology Study Group. The topics covered included: pulmonary toxicity, cardiac toxicity, radiotherapy dose, fractionation and volumes, unfit/elderly patients, multidisciplinary management. EXPERT OPINION: The debate was focused on the unmet needs triggered by case reports, personal experiences and questions; the answers were often not univocal; however, the exchange of opinion and the contribution of different centers confirmed the role of multidisciplinary management and the necessity that the most critical issues should be investigated in clinical trials.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Humans , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Neoplasm Staging , Pandemics , Radiation Oncologists
13.
Cytopathology ; 33(1): 23-38, 2022 01.
Article in English | MEDLINE | ID: covidwho-1799272

ABSTRACT

Lung cancer is a leading cause of cancer mortality worldwide but recent years have seen a rapidly rising proportion of cases of advanced non-small cell carcinoma amenable to increasingly targeted therapy, initially based on the differential response to systemic treatment of tumours of squamous or glandular differentiation. In two-thirds of the cases, where patients present with advanced disease, both primary pathological diagnosis and biomarker testing is based on small biopsies and cytopathological specimens. The framework of this article is an overview of the technical aspect of each stage of the specimen pathway with emphasis on maximising potential for success when using small cytology samples. It brings together the current literature addressing pre-analytical and analytical aspects of specimen acquisition, performing rapid onsite evaluation, and undertaking diagnostic and predictive testing using immunocytochemistry and molecular platforms. The advantages and drawbacks of performing analysis on cell block and non-cell block specimen preparations is discussed.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma , Lung Neoplasms , Biomarkers, Tumor/metabolism , Carcinoma/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung/pathology , Lung Neoplasms/pathology
14.
Front Public Health ; 9: 743558, 2021.
Article in English | MEDLINE | ID: covidwho-1775906

ABSTRACT

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cost-Benefit Analysis , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology
15.
Int J Mol Sci ; 23(6)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760653

ABSTRACT

Lung cancer (LC) is the leading cause of cancer-related death worldwide. Although the diagnosis and treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 80% of LC cases, have greatly improved in the past decade, there is still an urgent need to find more sensitive and specific screening methods. Recently, new molecular biomarkers are emerging as potential non-invasive diagnostic agents to screen NSCLC, including multiple microRNAs (miRNAs) that show an unusual expression profile. Moreover, peripheral blood mononuclear cells' (PBMCs) miRNA profile could be linked with NSCLC and used for diagnosis. We developed a molecular beacon (MB)-based miRNA detection strategy for NSCLC. Following PBMCs isolation and screening of the expression profile of a panel of miRNA by RT-qPCR, we designed a MB targeting of up-regulated miR-21-5p. This MB 21-5p was characterized by FRET-melting, CD, NMR and native PAGE, allowing the optimization of an in-situ approach involving miR-21-5p detection in PBMCs via MB. Data show the developed MB approach potential for miR-21-5p detection in PBMCs from clinical samples towards NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic , Humans , Leukocytes, Mononuclear/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , MicroRNAs/metabolism
16.
Cells ; 11(6)2022 03 12.
Article in English | MEDLINE | ID: covidwho-1742342

ABSTRACT

Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Cystic Fibrosis , Lung Neoplasms , COVID-19/genetics , COVID-19/therapy , Cystic Fibrosis/metabolism , Humans , Lung/metabolism
17.
Molecules ; 27(5)2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1737002

ABSTRACT

Rearranged during transfection (RET) is an oncogenic driver receptor that is overexpressed in several cancer types, including non-small cell lung cancer. To date, only multiple kinase inhibitors are widely used to treat RET-positive cancer patients. These inhibitors exhibit high toxicity, less efficacy, and specificity against RET. The development of drug-resistant mutations in RET protein further deteriorates this situation. Hence, in the present study, we aimed to design novel drug-like compounds using a fragment-based drug designing strategy to overcome these issues. About 18 known inhibitors from diverse chemical classes were fragmented and bred to form novel compounds against RET proteins. The inhibitory activity of the resultant 115 hybrid molecules was evaluated using molecular docking and RF-Score analysis. The binding free energy and chemical reactivity of the compounds were computed using MM-GBSA and density functional theory analysis, respectively. The results from our study revealed that the developed hybrid molecules except for LF21 and LF27 showed higher reactivity and stability than Pralsetinib. Ultimately, the process resulted in three hybrid molecules namely LF1, LF2, and LF88 having potent inhibitory activity against RET proteins. The scrutinized molecules were then subjected to molecular dynamics simulation for 200 ns and MM-PBSA analysis to eliminate a false positive design. The results from our analysis hypothesized that the designed compounds exhibited significant inhibitory activity against multiple RET variants. Thus, these could be considered as potential leads for further experimental studies.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Drug Design , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Molecular Docking Simulation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/genetics , Proto-Oncogene Proteins c-ret/therapeutic use
18.
PLoS One ; 17(2): e0264201, 2022.
Article in English | MEDLINE | ID: covidwho-1714776

ABSTRACT

Activating mutations in EGFR predict benefit from tyrosine kinase inhibitor therapy for patients with advanced non-small cell lung cancer. Directing patients to appropriate therapy depends on accurate and timely EGFR assessment in the molecular pathology laboratory. This article describes the analytical design, performance characteristics, and clinical implementation of an assay for the rapid detection of EGFR L858R and exon 19 deletion mutations. A droplet digital polymerase chain reaction (ddPCR) assay was implemented with probe hydrolysis-dependent signal detection. A mutation-specific probe was used to detect EGFR L858R. A loss of signal design was used to detect EGFR exon 19 deletion mutations. Analytical sensitivity was dependent on DNA input and was as low as 0.01% variant allele fraction for the EGFR L858R assay and 0.1% variant allele fraction for the EGFR exon 19 deletion assay. Correlation of 20 clinical specimens tested by ddPCR and next generation sequencing showed 100% concordance. ddPCR showed 53% clinical sensitivity in the detection of EGFR mutations in plasma cell-free DNA from patients with lung cancer. The median clinical turnaround time was 5 days for ddPCR compared to 13 days for next generation sequencing. The findings show that ddPCR is an accurate and rapid method for detecting EGFR mutations in patients with non-small cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis/methods , Lung Neoplasms/genetics , Polymerase Chain Reaction/methods , ErbB Receptors/genetics , Humans , Mutation , Sensitivity and Specificity
19.
J Thorac Cardiovasc Surg ; 164(2): 378-385, 2022 08.
Article in English | MEDLINE | ID: covidwho-1712841

ABSTRACT

BACKGROUND: The influence of SARS-CoV-2 on surgery for non-small cell lung cancer needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. OBJECTIVE: This study reports on the 90-day rate of infection as well as the morbidity and mortality of lung surgery for cancer in a tertiary care hospital located in a pandemic epicenter. METHODS: We conducted a retrospective review of a prospective database to identify consecutive patients who underwent lung cancer resection before (January 1, 2020-March 10, 2020, group 1; 57 patients) and during the COVID-19 pandemic (March 11, 2020-June 10, 2020, group 2; 41 patients). The primary end point was the occurrence of SARS-CoV-2 infection during the first 90-days after surgery. The secondary outcome measure was 90-day perioperative morbidity and mortality. RESULTS: Patient characteristics were not significantly different between the groups. Ninety-day COVID-19 infection rates was 7.3% (3 out of 41) for patients undergoing an operation during the pandemic and 3.5% (2 out of 57) in patients operated on immediately before the pandemic. All patients tested positive 10 to 62 days after the index surgical procedure following hospital discharge. Four COVID-19-positive patients were symptomatic and 4 out of 5 patients required hospitalization, were men, previous or current smokers with hyperlipidemia, and underwent a sublobar resection. Univariate analysis did not identify any differences in postoperative complications before or during the COVID-19 pandemic. Ninety-day mortality was 5% (2 out of 41) for lung cancer surgery performed during the pandemic, with all deaths occurring due to COVID-19, compared with 0% (0 out of 57) mortality in patients who underwent an operation before the pandemic. CONCLUSIONS: During the COVID-19 pandemic, COVID-19 infections occurred in 7.3% of patients who underwent surgery for non-small cell lung cancer. In this series all infections occurred after hospital discharge. Our results suggest that COVID-19 infections occurring within 90 days of surgery portend a 40% mortality, warranting close postoperative surveillance.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , COVID-19/epidemiology , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/surgery , Male , Pandemics , Retrospective Studies , SARS-CoV-2
20.
J Surg Res ; 274: 213-223, 2022 06.
Article in English | MEDLINE | ID: covidwho-1707290

ABSTRACT

INTRODUCTION: In the current era of episode-based hospital reimbursements, it is important to determine the impact of hospital size on contemporary national trends in surgical technique and outcomes of lobectomy. METHODS: Patients aged >18 y undergoing open and video-assisted thoracoscopic surgery (VATS) lobectomy from 2008 to 2014 were identified using insurance claims data from the National Inpatient Sample. The impact of hospital size on surgical approach and outcomes for both open and VATS lobectomy were analyzed. RESULTS: Over the 7-y period, 202,668 lobectomies were performed nationally, including 71,638 VATS and 131,030 open. Although the overall number of lobectomies decreased (30,058 in 2008 versus 27,340 in 2014, P < 0.01), the proportion of VATS lobectomies increased (24.0% versus 46.9%), and open lobectomies decreased (76.0% versus 53.0%, all P < 0.01). When stratified by hospital size, small hospitals had a significant increase in the proportion of open lobectomies (6.4%-12.2%; P = 0.01) and trend toward increased number of VATS lobectomies (2.7%-12.2%). Annual mortality rates for VATS (range: 1.0%-1.9%) and open (range: 1.9%-2.4%) lobectomy did not significantly differ over time (all P > 0.05) but did decrease among small hospitals (4.1%-1.3% and 5.1%-1.1% for VATS and open, respectively; both P < 0.05). After adjusting for confounders, hospital bed size was not a predictor of in-hospital mortality. CONCLUSIONS: Utilization of VATS lobectomies has increased over time, more so among small hospitals. Mortality rates for open lobectomy remain consistently higher than VATS lobectomy (range 0.4%-1.4%) but did not significantly differ over time. This data can help benchmark hospital performance in the future.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/surgery , Pneumonectomy/methods , Retrospective Studies , Thoracic Surgery, Video-Assisted/methods , Thoracotomy
SELECTION OF CITATIONS
SEARCH DETAIL