Project description:ObjectiveLung adenocarcinoma often includes noninvasive components with postoperative lepidic morphology on pathologic specimens that appear on preoperative high-resolution computed tomography (HRCT) images as ground-glass opacity (GGO). We aimed to disclose the role of GGO on the aggressiveness of pathologically confirmed pure invasive tumors in patients with early-stage lung adenocarcinoma.MethodsThe prognosis of 932 patients with clinical stage 0-IA and pathologic node-negative lung adenocarcinoma who underwent lobectomy at 3 institutions between 2010 and 2016 was investigated according to the status of GGO and lepidic components.ResultsThe recurrence-free survival (RFS) of patients with pathologically confirmed pure invasive tumors was worse without (n = 81) than with (n = 43) GGO (69.7%; 95% confidence interval [CI], 57.3%-79.2% vs 90.5%; 95% CI, 76.6%-96.3%, P = .028). The RFS of patients with radiologically confirmed pure solid tumors was worse without (n = 81), than with (n = 173) a lepidic component (69.7%; 95% CI, 57.3%-79.2% vs 85.3%; 95% CI, 77.2%-90.7%, P = .0012). Multivariable Cox regression analysis of overall survival and RFS revealed that pure solid and pure invasive tumors, respectively, determined by HRCT and pathologic assessment together comprised an independent prognostic factor like vascular or pleural invasion for patients with early-stage lung adenocarcinoma.ConclusionsTumors of non-small cell lung cancer with pure solid and pure invasive components were more aggressive than those with some GGO and lepidic components. Complementary HRCT and pathologic findings can predict the malignant aggressiveness of adenocarcinoma.
Project description:BackgroundIncreasing evidence suggests that ground-glass opacity featured lung adenocarcinoma (GGO-LUAD) and pure solid-LUAD have significantly different tumor biological behaviors; the former is usually indolent. Genetic variations fundamentally contribute to this distinct tumor behaviors. This study aims to investigate and compare the gene mutations using next-generation sequencing (NGS) technology in these two subtypes of LUAD.MethodsThe clinical data and gene testing results of 46 patients suffering from LUAD with a histologically invasive subtype ≤3 cm and operated in the Thoracic Surgery Department of Beijing Tsinghua Changgung Hospital from May 2019 to December 2022 were retrospectively analyzed; a case-control study was performed to compare the pathological and genetic differences between LUAD with a GGO component and pure solid-LUAD.ResultsNotable differences existed in vascular invasion, tumor spread through air spaces (STAS) and high-risk histological subtypes (micropapillary or solid subtypes) between the two types of LUAD with similar histologically invasive size. No significant difference was found in the mutation frequency of EGFR and KRAS. However, gene mutations were more prevalent in the cell cycle and TP53 signaling pathway for solid-LUAD. A significant difference was found in the mutation frequency of the tumor suppressor genes TP53 and CDKN2A between the two types.ConclusionsThe wild-type TP53 and CDKN2A genes could potentially be used as molecular indicators for indolent LUAD characterized by GGO-featured.
Project description:BackgroundAlthough subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group.MethodsPatients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses.ResultsA total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules.ConclusionsThe radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.
Project description:Introduction: Due to the introduction of low-dose computed tomography (CT) and screening procedures, the proportion of early-stage lung cancer with ground glass opacity (GGO) manifestation is increasing in clinical practice. However, its epidemiological characteristics is still not fully investigated. Methods: We retrieved all solitary GGO adenocarcinoma lung cancer (ADLC) on the PubMed, Cochrane Library, and Embase databases until January 1, 2019 and extracted the general information to perform the meta-analysis, mainly focusing on age, gender, and smoking status. Results: A total of 8,793 solitary GGO ADLC patients from 53 studies were included in this analysis. The final pooled analysis showed that the female proportion, average diagnosis age, and non-smoking proportion of solitary GGO ADLC was 0.62 (95% CI, 0.60-0.64), 56.97 (95% CI, 54.56-59.37), and 0.72 (95% CI, 0.66-0.77), respectively. The cumulative meta-analysis and meta-trend analysis confirmed that the average age at diagnosis has been decreasing while the non-smoking proportion significantly increased in the past two decades. Conclusions: From our epidemiological analysis, it demonstrates that the clinical characteristics of GGO lung cancer patients may be out of the high-risk factors. Therefore, we propose to reconsider the risk assessment and current lung cancer screening criteria.
Project description:BackgroundInvasive pure ground-glass opacity and pre-invasive pure ground-glass opacity have different 5-year overall survival rate and risk of lymph node metastasis and the extent of resection. It is difficult to discriminate these nodules since they share similar CT features and may occur concurrently. The objectives of this study were to investigate the feasibility of non-contrast enhanced plus contrast-enhanced computed tomography in discriminating invasive pure ground-glass opacity from pre-invasive pure ground-glass opacity.MethodsWe retrospectively examined 90 patients with pure ground-glass opacity who underwent non-contrast enhanced and contrast-enhanced CT according to a simplified protocol (one non-contrast enhanced measurement and two contrast-enhanced measurements at 30?s and 60?s after contrast injection) from 2015 to 2019. All imaging examinations were analyzed using three-dimensional computer-aided volume. Two independent samples t tests, one-way analysis of variance, chi-square test and logistic regression were used for analysis. A receiver operating characteristic curve was used to determine the optimal cut-off value of mean CT attenuation for differentiation of groups and to obtain diagnostic value.Results(1) The CT values of one non-contrast-enhanced, two contrast-enhanced and volume measurements between two groups had statistically significant differences (P <?0.001). (2) At the 30-s scan, there were more nodules in the pre-invasive group with no enhancement than in the pre-invasive group, which was statistically significant. (3) The CT value of 60-s scan was independent predictor of invasive adenocarcinoma (P =?0.019).ConclusionsNon-contrast enhanced plus two contrast-enhanced CT based on volume measurements can differentiate invasive pGGO from pre-invasive pGGO.
Project description:BACKGROUND:Lobectomy plus lymph node dissection is the standard treatment of early-stage lung cancer, but the low lymph node metastasis rate with ground-glass opacity (GGO) makes surgeons not perform lymphadenectomy. This study aimed to re-evaluate the lymph node metastasis rate of GGO to help make a clinical judgment. METHODS:We performed this retrospective study to enroll patients who received lung cancer surgery from 2011 to 2016. Patient characteristics collected included tumor size, solid part size and lymph node metastasis rate. These patients were categorized into pure GGO and part solid GGO groups to undergo analysis. RESULTS:Lymph node metastasis rates were 0%, 3.8% and 6.9% in order of the pure GGO group, the GGO predominant group and the solid predominant group. In the lobectomy patients, the solid predominant group still showed to have the highest lymph node metastasis rate and recurrence rate (8.3% and 10.1%). CONCLUSION:It is unnecessary to perform lymphadenectomy for patients with pure GGO in view of the 0% lymph node metastasis rate. The higher lymph node metastasis rate in the patients with the solid predominant group, 6.9%, suggested that surgeons should choose a rational lymphadenectomy method according to their GGO property and clinical judgment.
Project description:BackgroundLung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD.MethodsLUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in non- GGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted.ResultsOverall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation.ConclusionIn conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.
Project description:BackgroundThe prognostic value of ground glass opacity (GGO) in stage IA non-small cell lung cancer (NSCLC) has been widely recognized. However, studies investigating its value in the related stage IB-IIA lung adenocarcinoma (LUAD) remains lacking. The impact of adjuvant chemotherapy (ACT) on pathological stage IB-IIA LUAD is also controversial.Materials and methodsWe retrospectively reviewed the clinical records of 501 patients with pathological stage IB-IIA LUAD at the Sun Yat-sen University Cancer Center from January 2008 to June 2018. We calculated and compared survival curves using the Kaplan-Meier test and log-rank test. Cox regression models were performed to determine independent prognostic factors of disease-free survival (DFS) and overall survival (OS). We established nomograms to predict the OS and DFS of LUAD patients. Calibration and receiver operator characteristic curves were conducted to assess the predictive performance of two nomograms. Based on the nomogram, we identified candidate patients that may most benefit from ACT after surgery.ResultsThe number of patients with pure solid, part GGO, and pure GGO nodules was 240, 242, and 19, respectively, and 125 patients who received ACT. Patients with consolidation-to-tumor ratio (CTR) <0.75 had longer OS (P = 0.026) and DFS (P = 0.003). Pathological tumor size and at least 10 lymph nodes (LNs) resection were independent prognostic factors of both OS and DFS. CTR <0.75 was positively associated with DFS. The C-index of nomograms predicting individual OS and DFS was 0.660 and 0.634, respectively. Based on the nomogram for OS, ACT was found to be a positive prognostic indicator of OS (P = 0.031, HR = 0.5141, 95% CI 0.281-0.942) in patients with nomogram total points ≥5.ConclusionCTR <0.75 is associated with a better DFS in patients with stage IB-IIA LUAD. Nomograms developed by integrating pathological tumor size, at least 10 LNs resection, and CTR ≥0.75 for predicting individual OS and DFS displayed a good predictive capacity and clinical value, which were also proved to be a useful tool for selecting patients most benefiting from ACT.
Project description:BackgroundEarly-stage lung cancers radiologically manifested as ground-glass opacities (GGOs) have been increasingly identified, among which pure GGO (pGGO) has a good prognosis after local resection. However, the optimal surgical margin is still under debate. Precancerous lesions exist in tumor-adjacent tissues beyond the histological margin. However, potential precancerous epigenetic variation patterns beyond the histological margin of pGGO are yet to be discovered and described.ResultsA genome-wide high-resolution DNA methylation analysis was performed on samples collected from 15 pGGO at tumor core (TC), tumor edge (TE), para-tumor tissues at the 5 mm, 10 mm, 15 mm, 20 mm beyond the tumor, and peripheral normal (PN) tissue. TC and TE were tested with the same genetic alterations, which were also observed in histologically normal tissue at 5 mm in two patients with lower mutation allele frequency. According to the difference of methylation profiles between PN samples, 2284 methylation haplotype blocks (MHBs), 1657 differentially methylated CpG sites (DMCs), and 713 differentially methylated regions (DMRs) were identified using reduced representation bisulfite sequencing (RRBS). Two different patterns of methylation markers were observed: Steep (S) markers sharply changed at 5 mm beyond the histological margin, and Gradual (G) markers changed gradually from TC to PN. S markers composed 86.2% of the tumor-related methylation markers, and G markers composed the other 13.8%. S-marker-associated genes enriched in GO terms that were related to the hallmarks of cancer, and G-markers-associated genes enriched in pathways of stem cell pluripotency and transcriptional misregulation in cancer. Significant difference in DNA methylation score was observed between peripheral normal tissue and tumor-adjacent tissues 5 mm further from the histological margin (p < 0.001 in MHB markers). DNA methylation score at and beyond 10 mm from histological margin is not significantly different from peripheral normal tissues (p > 0.05 in all markers).ConclusionsAccording to the methylation pattern observed in our study, it was implied that methylation alterations were not significantly different between tissues at or beyond P10 and distal normal tissues. This finding explained for the excellent prognosis from radical resections with surgical margins of more than 15 mm. The inclusion of epigenetic characteristics into surgical margin analysis may yield a more sensitive and accurate assessment of remnant cancerous and precancerous cells in the surgical margins.