Aims:
Interstitial lung disease (ILD) is associated with the incidence of non-small cell lung cancer (NSCLC). Patients with ILD are at risk of acute exacerbation (AE) after pulmonary resection. ...However, there have been no recognized treatment guidelines for NSCLC patients with ILD on computed tomography (CT).
Methods:
We reviewed the medical records of 156 consecutive patients with ILD on high-resolution CT who have undergone pulmonary resection and between 2014 and 2018. Data regarding general information, imaging features, perioperative indicators, and long-term prognosis of patients were compared.
Results:
The mean patient age was 67.24 ± 6.80 years. Postoperative AE occurred in seven (4.5%) patients; five (71.4%) of the seven patients who had an AE died within 30 days. The incidence of postoperative AE was 5.3% among patients who underwent lobectomy (n = 6). Overall survivals (OS) was significantly poorer in patients with possible usual interstitial pneumonia (UIP)/UIP hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.11–4.95, p = 0.026 and severe postoperative complications (Grade ⩾3) (versus no complication: HR 2.58, 95% CI 1.11–6.02, p = 0.028; versus mild complications: HR 6.05, 95% CI 2.69–13.6, p < 0.001). Age (HR 1.071, 95% CI 1.006–1.137, p = 0.030) and ILD patterns (HR 2.420, 95% CI 1.024–5.716, p = 0.044) were independent prognostic factors for OS. Forced vital capacity (FVC) (odds ratio 0.351, 95% CI 0.145–0.850, p = 0.020) was an independent prognostic factor for patients who needed postoperative intensive care unit intervention.
Conclusion:
Pulmonary resection for NSCLC Patients with ILD on CT is a safe procedure. However, surgical indications for lobectomy need to be more carefully for these patients, especially for possible UIP/UIP patients and patients with lower FVC.
The reviews of this paper are available via the supplemental material section.
To evaluate whether quantitative features of persistent pure ground-glass nodules (PGGN) on the initial computed tomography (CT) scans can predict further nodule growth.
This retrospective study ...included 59 patients with 101 PGGNs from 2011 to 2012, who received regular CT follow-up for lung nodule surveillance. Nineteen quantitative image features consisting of 8 volumetric and 11 histogram parameters were calculated to detect lung nodule growth. For the extraction of the quantitative features, semi-automatic GrowCut segmentation was implemented on chest CT images in 3D slicer platform. Univariate and multivariate analyses were performed to identify risk factors for nodule growth.
With a median follow-up of 52 months, nodule growth was detected in 10 nodules by radiological assessment and in 16 nodules by quantitative features. In univariate analysis, 3D maximum diameter (MD), volume, mass, surface area, 90% percentile, and standard deviation value (SD) of PGGN on the initial CT scan were significantly different between stable nodules and nodules with further growth. In multivariate analysis, MD hazard ratio (HR), 3.75; 95% confidence interval (CI), 2.14-6.55 and SD (HR, 2.06; 95% CI, 1.35-3.14) were independent predictors of further nodule growth. Also, the area under the curve was 0.896 (95% CI: 0.820-0.948) and 0.813 (95% CI: 0.723-0.883) for MD with a cut-off value of 10.2mm and SD of 50.0 Hounsfield Unit (HU). Besides, the growth rate was 55.6% (n=15) of PGGNs with MD >10.2 mm and SD >50.0 HU.
Based on the initial CT scan, the quantitative features can predict PGGN growth more precisely. PGGN with MD >10.2 mm and SD >50.0 HU may require close follow-up or surgical intervention for the high incidence of growth.
Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs ...remain elusive.
We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES).
In the entire cohort, many known driver mutations were found, including
(21.7%),
(14.5%), and
(6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (
= 0.57). The CNV sizes were correlated with the somatic mutations (
= 0.55). A moderate correlation (
= 0.54) was also shown between the somatic and germline mutations.
Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens.
Emerging evidence indicates that extracellular vesicle (EV) long non-coding ribonucleic acids (lncRNAs) in lung cancer may be clinically useful biomarkers for early diagnosis using liquid biopsy. ...However, the extremely low quantities of EV-lncRNAs in peripheral blood are a major challenge for multi-target detection. In this study, we developed a new multi-colour fluorescence digital PCR EV-lncRNA (miDER) analysis chip, and then demonstrated its ability to quickly and accurately analyse the levels of two target genes and one reference gene from peripheral blood. Under the miDER assay, the limit of detection of the target gene from peripheral blood was 10 copies/μL. Based on multiplex assay, the expression levels of two lung cancer-related genes (SLC9A3-AS1 and PCAT6) in patients with lung cancer (n = 32) and healthy controls (n = 30) showed a significant difference between the two groups (P < 0.001; two-tailed t-test). A receiver operating characteristic (ROC) curve analysis was used to evaluate the discrimination ability of these lncRNAs. The combination of two lncRNAs in the miDER assay yielded a higher area under curve (AUC) value of 0.811 (95% CI = 0.705–0.918). Moreover, to determine the absolute quantitation capacity of the miDER assay, we compared the results to those obtained by quantitative real-time polymerase chain reaction (qPCR), demonstrating that the miDER assay is more sensitive than qPCR. The multiplex assay based on the miDER could provide a new solution for the multi-index combined detection of trace EV-lncRNAs in body fluids and demonstrate the use of EV-lncRNAs as biomarkers for lung tumour biopsy.
•A new multi-colour fluorescence digital PCR EV-lncRNA (miDER) analysis chip was developed.•The miDER system can simultaneously detect multi-target EV-lncRNAs.•The clinical blood samples were analysed and showed the potential of EV-lncRNAs as a candidate marker for lung cancer.
Chemokine receptor 4 (CXCR4) is a subtype receptor protein of the GPCR family with a seven-transmembrane structure widely distributed in human tissues. CXCR4 is involved in diseases (e.g., HIV-1 ...infection), cancer proliferation and metastasis, inflammation signaling pathways, and leukemia, making it a promising drug target. Clinical trials on CXCR4 antagonists mainly focused on peptides and antibodies, with a few small molecule compounds, such as AMD11070 (2) and MSX-122 (3), showing promise in cancer treatment. This perspective discusses the structure-activity relationship (SAR) of CXCR4 and its role in diseases, mainly focusing on the SAR of CXCR4 antagonists. It also explores the standard structural features and target interactions of CXCR4 binding in different disease categories. Furthermore, it investigates various modification strategies to propose potential improvements in the effectiveness of CXCR4 drugs.
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•Summary of CXCR4: structure, function, and its role in diseases.•Latest on CXCR4 antagonist progress & structure-activity relationship.•The development and future of CXCR4 small molecule antagonists.
Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and ...End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.
The eighth edition of nodal classification for non-small-cell lung cancer (NSCLC) is defined only by the anatomical location of metastatic lymph nodes.
We sought to evaluate the prognostic ...significance and discriminatory capability of the number of involved nodal stations (nS) in a large Chinese cohort.
A total of 4,011 patients with NSCLC undergoing surgical resection between 2009 and 2013 were identified. The optimal cutoff values for nS classification were determined with X-tile software. Kaplan-Meier and multivariate Cox analysis were used to examine the prognostic performance of nS classification in comparison with location-based N classification. A decision curve analysis was performed to evaluate the standardized net benefit of nS classification in predicting prognosis.
All the patients were classified into four prognostically different subgroups according to the number of involved nodal stations: (1) nS0 (none positive), (2) nS1 (one involved station), (3) nS2 (two involved stations), and (4) nS ≥ 3 (three or more involved stations). The prognoses among all the neighboring categories of nS classification were statistically significantly different in terms of disease-free survival and overall survival. The multivariate Cox analysis demonstrated that nS was an independent prognostic factor of disease-free survival and overall survival. Patients with N1 or N2 stage disease could be divided into three prognostically different subgroups according to nS classification. However, the prognosis was similar between the N1 and N2 subgroups when patients were staged in the same nS category. The decision curve analysis showed that nS classification tended to have a higher predictive capability than location-based N classification.
The nS classification could be used to provide a more accurate prognosis for patients with resected NSCLC. The nS is worth taking into consideration when defining nodal category in the forthcoming ninth edition of the staging system.
Tumor spread through air spaces (STAS) is a novel invasive pattern in lung adenocarcinoma (ADC). The effects of the combination of STAS and tumor size on survival have not been well studied.
A total ...of 383 patients with ADC 3 cm or smaller (stage IA) and 161 patients with stage IB ADC were identified from 2009 to 2010. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. A validation cohort was included in this study.
STAS was observed in 116 ADCs 3 cm or smaller (30.3%). In cases involving ADCs 3 cm or smaller, patients with STAS had worse RFS (p = 0.006) and OS rates (p < 0.001) than those without STAS. Furthermore, comparable RFS (p = 0.091) and OS (p = 0.443) rates were observed in patients with ADCs 3 cm or smaller with STAS present and those with stage IB ADC. Multivariate analysis revealed STAS to be an independent prognostic factor in ADCs 3 cm or smaller (RFS, p = 0.043; OS, p = 0.009). Among patients with ADCs larger than 2 to 3 cm, STAS still stratified the prognosis. Moreover, the unfavorable prognosis of patients with ADCs larger than 2 to 3 cm with STAS present was similar to that of patients with stage IB ADC. Among patients with ADCs 2 cm or smaller, STAS failed to stratify the prognosis significantly. Similar results were obtained in the validation cohort.
These results provide preliminary evidence that STAS could be considered as a factor in a staging system to predict prognosis more precisely, especially in ADCs larger than 2 to 3 cm.
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