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Introduction: To evaluate the effects of the global coronavirus disease 2019 (COVID-19) pandemic on lung cancer trials, we surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before and during the pandemic. Methods: A Data Collection Survey collected aggregate monthly enrollment numbers from 294 global lung cancer trials for 2019 to 2020. A 64-question Action Survey evaluated the impact of COVID-19 on clinical trials and identified mitigation strategies implemented. Results: Clinical trial enrollment declined from 2019 to 2020 by 14\% globally. Most reductions in enrollment occurred in April to June where we found significant decreases in individual site enrollment (p = 0.0309). Enrollment was not significantly different in October 2019 to December of 2019 versus 2020 (p = 0.25). The most frequent challenges identified by the Action Survey (N = 172) were fewer eligible patients (63\%), decrease in protocol compliance (56\%), and suspension of trials (54\%). Patient-specific challenges included access to trial site (49\%), ability to travel (54\%), and willingness to visit the site (59\%). The most frequent mitigation strategies included modified monitoring requirements (47\%), telehealth visits (45\%), modified required visits (25\%), mailorder medications (25\%), and laboratory (27\%) and radiology (21\%) tests at nonstudy facilities. Sites that felt the most effective mitigation strategies were telehealth visits (85\%), remote patient-reported symptom collection (85\%), off-site procedures (85\%), and remote consenting (89\%).Conclusions: The COVID-19 pandemic created many challenges for lung cancer clinical trials conduct and enrollment. Mitigation strategies were used and, although the pandemic worsened, trial enrollment improved. A more flexible approach may improve enrollment and access to clinical trials, even beyond the pandemic.(c) 2022 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.

Background In real-time RT quantitative PCR (qPCR) the accuracy of normalized data is highly dependent on the reliability of the reference genes (RGs). Failure to use an appropriate control gene for normalization of qPCR data may result in biased gene expression profiles, as well as low precision, so that only gross changes in expression level are declared statistically significant or patterns of expression are erroneously characterized. Therefore, it is essential to determine whether potential RGs are appropriate for specific experimental purposes. Aim of this study was to identify and validate RGs for use in the differentiation of normal and tumor lung expression profiles. Methods A meta-analysis of lung cancer transcription profiles generated with the GeneChip technology was used to identify five putative RGs. Their consistency and that of seven commonly used RGs was tested by using Taqman probes on 18 paired normal-tumor lung snap-frozen specimens obtained from non-small-cell lung cancer (NSCLC) patients during primary curative resection. Results The 12 RGs displayed showed a wide range of Ct values: except for rRNA18S (mean 9.8), the mean values of all the commercial RGs and ESD ranged from 19 to 26, whereas those of the microarray-selected RGs (BTF-3, YAP1, HIST1H2BC, RPL30) exceeded 26. RG expression stability within sample populations and under the experimental conditions (tumour versus normal lung specimens) was evaluated by: (1) descriptive statistic; (2) equivalence test; (3) GeNorm applet. All these approaches indicated that the most stable RGs were POLR2A, rRNA18S, YAP1 and ESD. Conclusion These data suggest that POLR2A, rRNA18S, YAP1 and ESD are the most suitable RGs for gene expression profile studies in NSCLC. Furthermore, they highlight the limitations of commercial RGs and indicate that meta-data analysis of genome-wide transcription profiling studies may identify new RGs.

The development of metastasis is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). Initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition (EMT). A central role for microRNA-200 family members in regulating EMT has been recently indicated, but data regarding the significance of their expression in lung tumors are still unavailable. The present study investigated the expression of mir-200c in a panel of NSCLC cell lines (n=9) and found a strong inverse correlation with cell invasive potential. Forced re-introduction of mir-200c into highly invasive/aggressive NSCLC cells induced a loss of mesenchymal phenotype, by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation, as evaluated by chicken embryo metastasis assay. Moreover, mir-200c overexpression restored the sensitivity towards cisplatin and cetuximab, two chemotherapeutic agents widely used in the treatments of thoracic cancers, of the drug-resistant NCI-H1299 cells. Hyper-methylation of the promoter region was found to be the mechanism behind the loss of mir-200c in invasive cells, as evaluated by 5-aza-dC treatment and methylation specific PCR. In primary tumor specimens obtained from 45 consecutively resected NSCLC patients, mir-200c expression confirmed its role in malignant tumor progression, being significantly inversely associated with a poor grade of differentiation (p=0.01) and a higher propensity to lymph node metastases (p Citation Information: Clin Cancer Res 2010;16(7 Suppl):A24