A pretreatment prediction model of grade 3 tumors classed by the IASLC grading system in lung adenocarcinoma.

PURPOSE: The new grading system for invasive nonmucinous lung adenocarcinoma (LUAD) in the 2021 World Health Organization Classification of Thoracic Tumors was based on a combination of histologically predominant subtypes and high-grade components. In this study, a model for the pretreatment prediction of grade 3 tumors was established according to new grading standards. METHODS: We retrospectively collected 399 cases of clinical stage I (cStage-I) LUAD surgically treated in Tianjin Chest Hospital from 2015 to 2018 as the training cohort. Besides, the validation cohort consists of 216 patients who were collected from 2019 to 2020. These patients were also diagnosed with clinical cStage-I LUAD and underwent surgical treatment at Tianjin Chest Hospital. Univariable and multivariable logistic regression analyses were used to select independent risk factors for grade 3 adenocarcinomas in the training cohort. The nomogram prediction model of grade 3 tumors was established by R software. RESULTS: In the training cohort, there were 155 grade 3 tumors (38.85%), the recurrence-free survival of which in the lobectomy subgroup was better than that in the sublobectomy subgroup (P = 0.034). After univariable and multivariable analysis, four predictors including consolidation-to-tumor ratio, CEA level, lobulation, and smoking history were incorporated into the model. A nomogram was established and internally validated by bootstrapping. The Hosmer-Lemeshow test result was χ2 = 7.052 (P = 0.531). The C-index and area under the receiver operating characteristic curve were 0.708 (95% CI: 0.6563-0.7586) for the training cohort and 0.713 (95% CI: 0.6426-0.7839) for the external validation cohort. CONCLUSIONS: The nomogram prediction model of grade 3 LUAD was well fitted and can be used to assist in surgical or adjuvant treatment decision-making.

Preoperative CT-based radiomics combined with tumour spread through air spaces can accurately predict early recurrence of stage I lung adenocarcinoma: a multicentre retrospective cohort study.

OBJECTIVE: To develop and validate a prediction model for early recurrence of stage I lung adenocarcinoma (LUAD) that combines radiomics features based on preoperative CT with tumour spread through air spaces (STAS). MATERIALS AND METHODS: The most recent preoperative thin-section chest CT scans and postoperative pathological haematoxylin and eosin-stained sections were retrospectively collected from patients with a postoperative pathological diagnosis of stage I LUAD. Regions of interest were manually segmented, and radiomics features were extracted from the tumour and peritumoral regions extended by 3 voxel units, 6 voxel units, and 12 voxel units, and 2D and 3D deep learning image features were extracted by convolutional neural networks. Then, the RAdiomics Integrated with STAS model (RAISm) was constructed. The performance of RAISm was then evaluated in a development cohort and validation cohort. RESULTS: A total of 226 patients from two medical centres from January 2015 to December 2018 were retrospectively included as the development cohort for the model and were randomly split into a training set (72.6%, n = 164) and a test set (27.4%, n = 62). From June 2019 to December 2019, 51 patients were included in the validation cohort. RAISm had excellent discrimination in predicting the early recurrence of stage I LUAD in the training cohort (AUC = 0.847, 95% CI 0.762-0.932) and validation cohort (AUC = 0.817, 95% CI 0.625-1.000). RAISm outperformed single modality signatures and other combinations of signatures in terms of discrimination and clinical net benefits. CONCLUSION: We pioneered combining preoperative CT-based radiomics with STAS to predict stage I LUAD recurrence postoperatively and confirmed the superior effect of the model in validation cohorts, showing its potential to assist in postoperative treatment strategies.

The value of frozen section diagnosis of tumor spread through air spaces in small-sized (≤ 2 cm) non-small cell lung cancer.

BACKGROUND: The current accuracy of frozen section diagnosis of tumor spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) is poor. However, the accuracy and prognostic value of STAS assessment on frozen sections in small-sized NSCLC (diameter ≤ 2 cm) is unknown. METHODS: Three hundred fifty-two patients with clinical stage I NSCLC (≤ 2 cm) were included, of which the paraffin sections and frozen sections were reviewed. The accuracy of STAS diagnosis in frozen sections was assessed using paraffin sections as the gold standard. The relationship between STAS on frozen sections and prognosis was assessed by the Kaplan-Meier method and log-rank tests. RESULTS: STAS on frozen sections in 58 of 352 patients could not be evaluated. In the other 294 patients, 36.39% (107/294) was STAS-positive on paraffin sections and 29.59% (87/294) on frozen sections. The accuracy of frozen section diagnosis of STAS was 74.14% (218/294), sensitivity was 55.14% (59/107), specificity was 85.02% (159/187) and agreement was moderate (K = 0.418). In subgroup analysis, the Kappa values for frozen section diagnosis of STAS in the consolidation-to-tumor ratio (CTR) ≤ 0.5 group and CTR > 0.5 group were 0.368, 0.415, respectively. In survival analysis, STAS-positive frozen sections were associated with worse recurrence-free survival in the CTR > 0.5 group (P < 0.05). CONCLUSIONS: The moderate accuracy and prognostic significance of frozen section diagnosis of STAS in clinical stage I NSCLC (≤ 2 cm in diameter; CTR > 0.5) suggests that frozen section assessment of STAS can be applied to the treatment strategy of small-sized NSCLC with CTR > 0.5.

Kremen2 drives the progression of non-small cell lung cancer by preventing SOCS3-mediated degradation of EGFR.

BACKGROUND: The transmembrane receptor Kremen2 has been reported to participate in the tumorigenesis and metastasis of gastric cancer. However, the role of Kremen2 in non-small cell lung cancer (NSCLC) and the underlying mechanism remain unclear. This study aimed to explore the biological function and regulatory mechanism of Kremen2 in NSCLC. METHODS: The correlation between Kremen2 expression and NSCLC was assessed by analyzing the public database and clinical tissue samples. Colony formation and EdU assays were performed to examine cell proliferation. Transwell and wound healing assays were used to observe cell migration ability. Tumor-bearing nude mice and metastatic tumor models were used to detect the in vivo tumorigenic and metastatic abilities of the NSCLC cells. An immunohistochemical assay was used to detect the expression of proliferation-related proteins in tissues. Western blot, immunoprecipitation and immunofluorescence were conducted to elucidate the Kremen2 regulatory mechanisms in NSCLC. RESULTS: Kremen2 was highly expressed in tumor tissues from NSCLC patients and was positively correlated with a poor patient prognosis. Knockout or knockdown of Kremen2 inhibited cell proliferation and migration ability of NSCLC cells. In vivo knockdown of Kremen2 inhibited the tumorigenicity and number of metastatic nodules of NSCLC cells in nude mice. Mechanistically, Kremen2 interacted with suppressor of cytokine signaling 3 (SOCS3) to maintain the epidermal growth factor receptor (EGFR) protein levels by preventing SOCS3-mediated ubiquitination and degradation of EGFR, which, in turn, promoted activation of the PI3K-AKT and JAK2-STAT3 signaling pathways. CONCLUSIONS: Our study identified Kremen2 as a candidate oncogene in NSCLC and may provide a potential target for NSCLC treatment.

Bibliometric analysis of global research trends on small-cell lung cancer (2012-2021).

Background: Small-cell lung cancer (SCLC) is a recalcitrant tumor with a poor prognosis. With the rise of SCLC research in the past decade, this study aims to analyze the foundation and frontiers of SCLC research through bibliometric analysis. Methods: Relevant publications from the Web of Science Core Collection were retrieved on January 3, 2022. R package bibliometrix and EXCEL2019 were used to analyze quantitative variables. Bibliometric mapping was constructed by VOS viewer and CiteSpace software to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords. Results: A total of 2,361 publications related to SCLC were identified with the total amount of articles steadily increasing, where China is the most productive country with 859 papers. Scholars and organizations from the United States, China, and Europe are primary sources of this research, among which the University of Texas MD Anderson Cancer Center made the most contribution to the field with 122 papers. Lung Cancer published the highest number of SCLC-related articles with a total of 121, while the Journal of Thoracic Oncology received the most citations totaling 3,098. Rudin, Charles M., and Sage, Julien are the most creative author. Leora, Horn, 2018, New Engl J Med and Rudin, Charles M., Nat Genet, 2012 can be categorized as classic literature owing to their high citations or strong sigma value. "Heterogeneity & Subtypes" and "Immunotherapy" may be the new frontiers in the SCLC domain. Conclusion: Research on SCLC showed an upward trend based on the current global situation. Moreover, the current scope of collaboration in SCLC research is chiefly regional, which should further focus on transnational cooperation in the future. More attention should be devoted to "Heterogeneity & Subtypes" and "Immunotherapy", which will be the hotspots in future research.

Impact of preoperative biopsy on tumor spread through air spaces in stage I non-small cell lung cancer: a propensity score-matched study.

BACKGROUND: Percutaneous needle biopsy (PNB) and bronchoscopic biopsy (BB) are widely used in the preoperative diagnosis of pulmonary nodules, but whether PNB or BB may cause tumor spread through air spaces (STAS) has not been reported. METHODS: 433 postoperative patients with pathological stage I non-small cell lung cancer (NSCLC) from January 2015 to December 2018 at our hospital were enrolled and divided into PNB group (n = 40), BB group (n = 48) and non-biopsy group (n = 345). The PNB and BB groups were matched using propensity score matched (PSM) separately from the non-biopsy group, after which the effects of PNB and BB on STAS, recurrence-free survival (RFS) and overall survival (OS) were assessed. RESULTS: After PSM for 9 confounding factors (gender, age, smoking history, tumor site, scope of surgery, pathology type, stage, maximum tumor diameter and postoperative treatment), 38 cases in the PNB group were successfully matched with 38 cases in the non-biopsy group and 28 cases in the BB group were successfully matched with 28 cases in the non-biopsy group. After PSM, there was no significant difference in the incidence of STAS between the PNB and non-biopsy groups (42.1% vs. 34.2%, P > 0.05) and between the BB and non-biopsy groups (42.9% vs. 46.4%, P > 0.05). The results after PSM showed no significant effect of both PNB and BB on RFS and OS after radical surgery (P > 0.05). CONCLUSION: Preoperative biopsy in patients with stage I NSCLC has not been shown to increase the occurrence of STAS, nor postoperative recurrence and death.

Pretreatment prediction of tumour spread through air spaces in clinical stage I non-small-cell lung cancer.

OBJECTIVES: The aim of this study was to construct a nomogram prediction model for tumour spread through air spaces (STAS) in clinical stage I non-small-cell lung cancer (NSCLC) and discuss its potential application value. METHODS: A total of 380 patients with clinical stage I NSCLC in Tianjin Chest Hospital were collected as the training cohort and 285 patients in Fujian Provincial Hospital were collected as the validation cohort. Univariable and multivariable logistic regression analyses were performed to determine independent factors for STAS in the training cohort. Based on the results of the multivariable analysis, the nomogram prediction model of STAS was constructed by R software. RESULTS: The incidence of STAS in the training cohort was 39.2%. STAS was associated with worse overall survival and recurrence-free survival (P < 0.01). Univariable analysis showed that maximum tumour diameter, consolidation-to-tumour ratio, spiculation, vacuole and carcinoembryonic antigen were associated with STAS (P < 0.05). Multivariable analysis showed that maximum tumour diameter, consolidation-to-tumour ratio, spiculation sign and vacuole were independent risk factors for STAS (P < 0.05). Based on this, the nomogram prediction model of STAS in clinical stage I NSCLC was constructed and internally validated by bootstrap. The Hosmer-Lemeshow test showed a χ2 value of 7.218 (P = 0.513). The area under the receiver operating characteristic curve and C-index were 0.724 (95% confidence interval: 0.673-0.775). The external validation conducted on the validation cohort produced an area under the receiver operating characteristic curve of 0.759 (95% confidence interval: 0.703-0.816). CONCLUSIONS: The constructed nomogram prediction model of STAS in clinical stage I NSCLC has good calibration and can potentially be applied to guide treatment selection.

Somatic mutations combined with clinical features can predict the postoperative prognosis of stage IIIA lung adenocarcinoma.

Background: Prognostic factors for stage IIIA lung adenocarcinoma (LUAD) are unclear. The current main treatment for stage IIIA LUAD is still controversial. Some Clinicians advocate synchronous chemoradiotherapy as the main treatment for stage IIIA LUAD. In contrast, some clinicians argue that there are still certain patients with stage IIIA LUAD who have a better postoperative prognosis. This study aimed to analyze preoperative factors as well as the association between somatic mutations and prognosis in stage IIIA LUAD [including overall survival (OS) time and the risk of postoperative recurrence]. Methods: This study retrospectively reviewed the data of patients with stage IIIA LUAD who underwent radical resection of lung cancer in the thoracic surgery department of Tianjin Chest Hospital from January 01, 2011 to September 30, 2016. All patients involved in the study provided written informed consent. The associations between OS and DFS and the clinical characteristics as well as somatic mutations of patients were analyzed separately. The Kaplan-Meier method was used for univariate analysis, and survival curves were drawn. Multivariate analysis was performed by the Cox regression model. Results: For univariate analysis, the prognostic factors of OS were the level of preoperative CYFRA21-1, the number of metastatic lymph node stations (NMLS), maximum tumor diameter, EGFR (epidermal growth factor receptor) classical base mutations, and the number of copies of POLE (polymerase epsilon) mutation (NCPM). Preoperative total protein level, preoperative CYFRA21-1 level, the number of metastatic lymph nodes (NMLN), maximum tumor diameter, the number of mutated genes (NMG) in tumor samples, TP53 mutations, and the number of copies of POLE mutation (NCPM) were associated with disease-free survival (DFS). The multivariate analysis showed that the preoperative CYFRA21-1 level, the number of metastatic lymph node stations (NMLS), and EGFR typical base mutations were independent prognostic factors of OS. The number of mutated genes (NMG), EGFR classical base mutations, preoperative NSE level, maximum tumor diameter, and the number of metastatic lymph node stations (NMLS) were independent prognostic factors for DFS. Conclusions: The preoperative level of tumor markers, the number of metastatic lymph node stations, and EGFR typical base mutations are important factors for the prognosis of patients with resectable stage IIIA LUAD.

Prognosis of the second predominant subtype in lung adenocarcinoma: a retrospective single-center cohort study.

Background: The histologic classification of lung adenocarcinoma (LUAD) was mainly divided into three pathological subtype groups: the low-grade predominant subtype group (lepidic), the intermediate-grade predominant subtype group (papillary and acinar), and the high-grade predominant subtype group (micropapillary and solid). Previous studies have focused on the prognostic impact of predominant subtypes of lung adenocarcinoma. In this investigation, we investigated the effect of the second predominant subtype on prognosis. Methods: The data of LUAD postoperative patients were retrospectively collected. Exclusion criteria included cases in which the pathologic results revealed a single characteristic, the presence of invasive mucinous LUAD, or if the first predominant and the second predominant groups could not be distinguished. Categorical variables were compared with the two-tailed Pearson χ2 test and continuous variables with the Student's t-test. Follow-up was conducted by telephone and other methods. Independent prognostic factors of the second major subtype were determined by the Kaplan-Meier method and log-rank test. The Cox proportional risk regression model was used to analyze the possible prognostic factors. Results: Among 293 patients, the mean age was 61.9 years and 47.1% were male. The results revealed that when the predominant group was the low-grade group, the second predominant groups had no significant influence on overall survival (OS) (P=0.15) but significantly influenced disease free survival (DFS) (P=0.037). Subsequently, when the predominant group was the intermediate-grade group, the second predominant groups significantly influenced OS (P=0.024) but had no significant influence on DFS (P=0.3). Moreover, when the predominant group was the high-grade group, the second predominant groups significantly influenced OS (P=0.033) but had no significant influence on DFS (P=0.31). Conclusions: The independent prognostic effect of the second predominant group was not identified for OS and DFS of lung adenocarcinoma. The effects of the second predominant subtype groups on OS and DFS were not evenly distributed among different predominant subtype groups, and the low-grade second predominant subtype exhibited some protective effects on the middle-grade predominant subtypes.

Safety and efficacy of lobectomy combined with off-pump coronary artery bypass grafting for lung cancer.

BACKGROUND: This study sought to assess the safety and efficacy of a lobectomy combined with off-pump coronary artery bypass grafting (OPCABG) among patients with lung cancer. METHODS: Patients who underwent a simultaneous pulmonary lobectomy combined with OPCABG at Tianjin Chest Hospital from December 2010 to June 2019 and patients who underwent pulmonary lobectomy during the same period were selected at a ratio of 1:2 using a multi-factor propensity score for this study. The clinical data of each group during the operation and perioperative period were analyzed and compared, and the survival curves were drawn using the Kaplan-Meier method to compare the long-term survival of the patients. RESULTS: In the simultaneous-surgery group, no patients required a secondary thoracotomy for hemostasis and there were no perioperative deaths; however, 2 patients underwent a second intubation, 2 patients underwent a second debridement and suturing due to wound infection, 28 patients (76.3%) had pulmonary complications, and 10 patients (26.3%) had circulatory complications. The operation time, intraoperative blood loss, postoperative drainage volume, postoperative hospital stay, and complication rate were all higher in the simultaneous-surgery group than the lobectomy group. No significant difference was observed in the long-term survival rates between the 2 groups. CONCLUSIONS: The simultaneous surgery was safe and effective. Some differences existed in the data between the 2 groups during the perioperative period; however, the risk of complications after surgery was controllable.