Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Clinical significance of baseline Epstein-Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

Rapid Identification of Three Gram-Negative Bacteria by Surface-Enhanced Raman Spectroscopy.

Gram-negative bacteria had been regarded as several important sources of lethal infection. Rapid identification of pathogenic bacteria is extremely important for the diagnosis and clinical treatment of diseases. In current study, three gram-negative bacteria, including Klebsiella aerogenes, Enterobacter cloacae and Escherichia coli, were used to access the feasibility of characterizing Gram-negative bacteria by surface-enhanced Raman Spectroscopy (SERS). Bacterial samples were from Escherichia coli isolates (n=1000), Klebsiella aerogenes isolates (n=1000) and Enterobacter cloacaeand isolates (n=1000). The differences of three Gram-negative bacteria were characterized by SERS spectra. Furthermore, four multivariate statistical algorithms based on the combination of principal component analysis (or partial least squares) and linear discriminant analysis (or support vector machine) were used to discriminate the spectra of three gram-negative bacteria.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

"Capsule drape wrap"-a new technology for iridoschisis management during phacoemulsification.

AIM: To introduce a new technique for iridoschisis management during phacoemulsification: "capsule drape wrap". METHODS: "Capsule drape wrap" technique was used for an 80-year-old man with idiopathic iridoschisis in the right eye during phacoemulsification. The inserted flexible nylon iris hooks to hold anterior capsule in place, the margin of the anterior capsule could act as drape wrap, tracking the fibrillary iris strands firmly from free floating and stabilizing the capsular bags simultaneously. RESULTS: The eye with iridoschisis was successfully treated. Iris fibrils remained immobile during the procedure, and despite the severity of iridoschisis, there were no intraoperative complications such as tear of the iris, hyphema, iris prolapse, loss of mydriasis, or rupture of the posterior lens capsule during phacoemulsification. The best-corrected visual acuity was increased by 0.1 (logMAR) 6mo after the surgery. CONCLUSION: "Capsule drape wrap" for iridoschisis is easily manageable, prevents further disruption to the loose iris fibers and ensures the stability of capsule-iris complex simultaneously, consequently minimizing the risk of surgical complications in phacoemulsification.

The independent prognostic effect of marital status on non-small cell lung cancer patients: a population-based study.

Background: Previous studies had demonstrated that marital status was an independent prognostic factor in multiple cancers. However, the impact of marital status on non-small cell lung cancer (NSCLC) patients was still highly controversial. Method: All NSCLC patients diagnosed between 2010-2016 were selected from the Surveillance, Epidemiology and End Results (SEER) database. To control the confounding effect of related clinicopathological characteristics, propensity score matching (PSM) was conducted between married and unmarried groups. In addition, independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression. Moreover, nomograms were established based on the clinicopathological characteristics, and the predictive accuracy was assessed by calibration curves. Furthermore, decision curve analysis (DCA) was used to determine the clinical benefits. Results: In total, 58,424 NSCLC patients were enrolled according to the selection criteria. After PSM, 20,148 patients were selected into each group for further analysis. The married group consistently demonstrated significantly better OS and CSS compared to unmarried group [OS median survival (95% CI): 25 (24-26) vs. 22 (21-23) months, p < 0.001; CSS median survival (95% CI): 31 (30-32) vs. 27 (26-28) months, p < 0.001]. Moreover, single patients were associated with the worst OS [median survival (95% CI): 20 (19-22) months] and CSS [median survival (95%CI): 24 (23-25) months] among unmarried subgroups. Besides, unmarried patients had a significantly worse prognosis compared to married patients in both univariate and multivariate Cox proportional hazard regressions. Furthermore, married group was associated with better survival in most subgroups. To predict the 1-, 3- and 5-year OS and CSS probabilities, nomograms were established based on age, race, sex, gender, marital status, histology, grade, TNM stage. The C-index for OS and CSS were 0.759 and 0.779. And the calibration curves showed significant agreement between predictive risk and the observed probability. DCA indicated nomograms had consistently better predict performance. Conclusion: This study demonstrated that unmarried NSCLC patients were associated with significantly worse OS and CSS compared to married NSCLC patients. Therefore, unmarried patients need not only closer surveillance, but also more social and family support, which may improve patients' adherence and compliance, and eventually improve the survival.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Background: Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Methods: Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. Results: A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). Conclusions: L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.

Invasiveness assessment by artificial intelligence against intraoperative frozen section for pulmonary nodules ≤ 3 cm.

PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.

CNS efficacy of afatinib as first-line treatment in advanced non-small cell lung cancer patients with EGFR mutations.

Background: Afatinib is a potent, irreversible second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has demonstrated efficacy in advanced non-small cell lung cancer (NSCLC) patients harboring either common or uncommon EGFR mutations. However, data on its activity against brain metastases are limited. This study aimed to retrospectively evaluate the efficacy and safety of afatinib as first-line treatment for EGFR-mutant NSCLC patients with brain metastases. Methods: Treatment-naive advanced NSCLC patients harboring EGFR mutations and brain metastases treated with afatinib were retrospectively reviewed to assess the central nervous system (CNS) efficacy and also the systematic benefits. Results: Totally 43 patients with measurable or non-measurable brain metastases were enrolled in the CNS full analysis (cFAS) set. Among them, 23 patients with measurable brain metastases were included in the CNS evaluable for response (cEFR) set. The CNS ORR was 48.8% (95% CI, 33.3 - 64.5%) in the cFAS set and 82.6% (95% CI, 61.2 - 95.0%) in the cEFR set, respectively. CNS mDoR was 8.9 months (95% CI, 4.7 - 13.1 months) and CNS mPFS was 12.7 months (95% CI, 6.9 - 18.5 months) in the cFAS set. In the subgroup analysis stratified by EGFR mutation types, CNS ORR of cEFR set in the common mutation cohort was 100% (95% CI, 75.3 - 100%) and 60% (95% CI, 26.2 - 87.8%) in the uncommon mutation cohort (p = 0.024); CNS ORR of cFAS set was 57.7% (95% CI, 36.9 - 76.6%) and 35.3% (95% CI, 14.2 - 61.7%), respectively (p = 0.151). CNS mPFS was 14.4 months in patients with common mutations and 6.1 months in patients with uncommon mutations (hazard ratio, 0.47; 95% CI, 0.22 - 1.00; p = 0.045). Patients with common mutations showed a significantly lower cumulative incidence of CNS failure than uncommon mutation cohort (p = 0.0026). Most of patients experienced grade 1/2 treatment-related adverse events. Conclusions: First-line afatinib demonstrated encouraging efficacy on brain metastases in NSCLC patients harboring either common or major uncommon EGFR mutations in a real-world setting, with manageable toxicities. Patients with common mutations showed better CNS outcomes than those with uncommon mutations.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods: Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results: A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions: This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

Ferroptosis-related lncRNAs signature to predict the survival and immune evasion for lung squamous cell carcinoma.

Introduction: the investigation on the interactions between ferroptosis and lncRNAs for lung squamous cell carcinoma (LUSC) has been scare, and its impact on tumor immune microenvironment remained unknown. We aim to not only identify a ferroptosis-related lncRNAs signature for LUSC prognosis, but also evaluate its correlation to tumor immune evasion. Methods: RNA sequencing data and survival information were obtained from The Cancer Genome Atlas database. A ferroptosis-related lncRNAs signature (FerRLSig) was developed and validated by univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression and multivariate Cox regression. The tumor immune microenvironment and immune evasion were subsequently evaluated based on the FerRLSig stratification. Results: the FerRLSig consisted of 10 ferroptosis-related lncRNAs and significantly associated with overall survival with satisfactory area under curve (HR = 2.240, 95% CI: 1.845-2.720, p < 0.001, 5-years AUC: 0.756). Based on the FerRLSig stratification, the high-risk group demonstrated not only significantly higher immune infiltration, but also more profound T cell dysfunction and immune evasion, which might ultimately lead to the resistance to current immune checkpoint inhibitors. Conclusion: a robust prognostic FerRLSig for LUSC has been developed and validated, demonstrating a close association not only with tumor immune cell infiltration, but also with T cell dysfunction and immune evasion. Further investigation is warranted to better improve the survival of LUSC patients based on the FerRLSig stratification.

Mutation-Derived Long Noncoding RNA Signature Predicts Survival in Lung Adenocarcinoma.

Background: Genomic instability is one of the representative features of cancer evolution. Recent research has revealed that long noncoding RNAs (lncRNAs) play a critical role in maintaining genomic instability. Our work proposed a gene signature (GILncSig) based on genomic instability-derived lncRNAs to probe the possibility of lncRNA signatures as an index of genomic instability, providing a potential new approach to identify genomic instability-related cancer biomarkers. Methods: Lung adenocarcinoma (LUAD) gene expression data from an RNA-seq FPKM dataset, somatic mutation information and relevant clinical materials were downloaded from The Cancer Genome Atlas (TCGA). A prognostic model consisting of genomic instability-related lncRNAs was constructed, termed GILncSig, to calculate the risk score. We validated GILncSig using data from the Gene Expression Omnibus (GEO) database. In this study, we used R software for data analysis. Results: Through univariate and multivariate Cox regression analyses, five genomic instability-associated lncRNAs (LINC01671, LINC01116, LINC01214, lncRNA PTCSC3, and LINC02555) were identified. We constructed a lncRNA signature (GILncSig) related to genomic instability. LUAD patients were classified into two risk groups by GILncSig. The results showed that the survival rate of LUAD patients in the low-risk group was higher than that of those in the high-risk group. Then, we verified GILncSig in the GEO database. GILncSig was associated with the genomic mutation rate of LUAD. We also used GILncSig to divide TP53 mutant-type patients and TP53 wild-type patients into two groups and performed prognostic analysis. The results suggested that compared with TP53 mutation status, GILncSig may have better prognostic significance. Conclusions: By combining the lncRNA expression profiles associated with somatic mutations and the corresponding clinical characteristics of LUAD, a lncRNA signature (GILncSig) related to genomic instability was established.

Analysis of the tumor immune environment identifies an immune gene set-based prognostic signature in non-small cell lung cancer.

BACKGROUND: The tumor immune environment plays a critical role in lung cancer initiation and prognosis. Therefore, understanding how the tumor immune environment impacts the overall survival (OS) of patients with advanced lung cancer post immunotherapy is of great importance. In this article, we aimed to identify the immune components of lung cancer and develop an immune prognostic signature to predict OS. METHODS: Differentially expressed immune-related genes were calculated between tumor and normal tissues using expression data from The Cancer Genome Atlas (TCGA) database. Then univariate Cox regression analysis was conducted to select prognosis-related genes and the prognostic risk model was constructed by multivariate Cox regression analysis. Patient risk scores were calculated, and a clinical correlation analysis was performed within the risk model. In addition, immune cell infiltration patterns were identified to find the immune cell subtypes related to prognosis. RESULTS: A gene model consisting of 12 immune-related genes was used as our signature. The model showed that the high-risk group experienced a shorter survival time, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.733. High-risk immune genes, such as S100 calcium binding protein A16 (S100A16) and angiopoietin-like 4 (ANGPTL4), were associated with more malignant clinical manifestations. Further, we discovered that extensive infiltration of B cells, dendritic cells, and mast cells indicated a favorable prognosis. CONCLUSIONS: The signature developed in this paper could be an effective model for estimating OS in lung cancer patients, and the immune cell infiltration analysis of the tumor immune microenvironment could shed light on more effective treatment in clinical practice.

The Independent Prognostic Effect of Lymph Node Dissection on Patients With Stage IA NSCLC With Different T Stages.

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC. Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1-2, 3-8, and ≥9 lymph nodes) and 3 groups (0, 1-3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis. Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438-0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476-0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups. Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer.

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248).

Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein.

BACKGROUND: RNA-binding proteins (RBPs) have been found to participate in the development and progression of cancer. This present study aimed to construct a RBP-based prognostic prediction model for lung adenocarcinoma (LUAD). METHODS: RNA sequencing data and corresponding clinical information were acquired from The Cancer Genome Atlas (TCGA) and served as a training set. The prediction model was validated using the dataset in Gene Expression Omnibus (GEO) databases. Univariate and multivariate Cox regression analyses were conducted to identify the RBPs associated with survival. R software (http://www.r-project.org) was used for analysis in this study. RESULTS: Nine hub prognostic RBPs (CIRBP, DARS2, DDX24, GAPDH, LARP6, SNRPE, WDR3, ZC3H12C, ZC3H12D) were identified by univariate Cox regression analysis and multivariate Cox regression analysis. Using a risk score based on the nine-hub RBP model, we separated the LUAD patients into a low-risk group and a high-risk group. The outcomes revealed that patients in the high-risk group had poorer survival than those in the low-risk group. This signature was validated in the GEO database. Further study revealed that the risk score can be an independent prognostic biomarker for LUAD. A nomogram based on the nine hub RBPs was built to quantitatively predict the prognosis of LUAD patients. CONCLUSIONS: Our nine-gene signature model could be used as a marker to predict the prognosis of LUAD and has potential for use in treatment individualization.

Segmental resection is associated with decreased survival in patients with stage IA non-small cell lung cancer with a tumor size of 21-30 mm.

BACKGROUND: The feasibility of segmental resection for early-stage non-small cell lung cancer (NSCLC) is still controversial. This study aimed to compare survival outcomes following lobectomy and segmental resection in patients with pathological T1cN0M0 (tumor size 21-30 mm) NSCLC. METHODS: Patients diagnosed between 1998 and 2016 with pathological stage IA NSCLC and with tumors measuring 21-30 mm were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The observational outcomes were cancer-specific survival (CSS) and overall survival (OS) at 5 years. Univariate survival analysis was carried out to identify potential prognostic factors of prolonged survival. Cox proportional hazards model was used to adjust for confounding factors. Additionally, pairwise comparisons were conducted between lobectomy and segmental resection for CSS and OS, and forest plots were drawn. RESULTS: Of the 9,580 patients analyzed, 400 patients (4.2%) underwent segmental resections. Patients with older age (P<0.001), smaller tumors (P<0.001), and left-sided tumors (P=0.002) were more likely to receive segmental resection. No difference was found in the operative mortality rates between the segmental resection group and the lobectomy group (1.0% vs. 1.2%, P=0.707). The CSS (HR, 1.429; 95% CI, 1.166-1.752; P=0.001) and OS (HR, 1.348; 95% CI, 1.176-1.544; P<0.001) in the segmental resection group were significantly worse than those in the lobectomy group. Subgroup analyses by age, year of diagnosis, sex, tumor size, histology, grade, and the number of dissected lymph nodes also confirmed that lobectomy was associated with improved CSS and OS. CONCLUSIONS: Lobectomy and thorough removal of lymph nodes should continue to be the recommended standard of care for patients with surgically resectable stage IA NSCLC with tumor size of 21-30 mm.

Development and validation of a preoperative noninvasive predictive model based on circular tumor DNA for lymph node metastasis in resectable non-small cell lung cancer.

BACKGROUND: Clinical lymph node staging in resectable non-small cell lung cancer (NSCLC) patients not only indicates prognosis, but also determines primary treatment strategy. The demand of noninvasive tool for preoperative lymph node metastasis prediction remains significant. This study aimed to develop and externally validate a preoperative noninvasive predictive model based on circular tumor DNA (ctDNA) for the lymph node metastasis in resectable NSCLC patients. METHODS: Resectable NSCLC patients in TRACERx cohort were included as training group. Potential preoperative noninvasively accessible predictors were incorporated into the development of a nomogram via multivariate logistic regression. The predictive model was externally validated by a similar cohort from our hospital. RESULTS: Overall, 58 patients from TRACERx cohort were included as training group and 37 patients from our hospital were included as external validation group. Variant allele frequency (VAF) level of ctDNA was significantly associated with lymph node metastasis (OR: 4.89, 95% CI: 1.22-19.54, P=0.03). The predictive model incorporating age, tumor size and VAF demonstrated satisfactory discrimination and calibration in both training group (AUC =0.77, 95% CI: 0.65-0.90, P=0.001) and external validation group (AUC =0.84, 95% CI: 0.70-0.99, P=0.005). CONCLUSIONS: High VAF level in preoperative ctDNA may indicate lymph node metastasis of resectable NSCLC. And a preoperative noninvasive predictive model based on ctDNA for the lymph node metastasis in resectable NSCLC patients was developed and externally validated with satisfactory discrimination and calibration.

[Feasibility of injecting Fluorescent Agent under the Guidance of Electromagnetic Navigation Bronchoscopy in Pulmonary Nodule Resection].

BACKGROUND: It is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. The purpose of this study is to explore the feasibility and necessity of the localization of pulmonary nodules by injecting indocyanine green (ICG) under the guidance of magnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope. METHODS: Between December 2018 and August 2019, sixteen consecutive patients with 30 peripheral lung lesions in our hospital received fluorescent thoracoscopic pulmonary nodule resection. Electromagnetic navigation bronchoscope (ENB) was performed before surgery to guide ICG to the target lesion. RESULTS: All patients underwent magnetic navigation-guided pulmonary nodule localization, and surgical resection was performed immediately after localization was completed. The average size of the nodules was (11.12±3.65) mm. The average navigation time was (12.06±2.74) minutes, and the average interval between dye labeling and lung resection was (25.00±5.29) minutes. All lesions were completely resected, the localization success rate was 100.00%, no bleeding and other complications occurred after the localization, the postoperative pathological results confirmed the accuracy of the staining. CONCLUSIONS: Indocyanine green injection under the guidance of magnetic navigation bronchoscope is an effective way to locate pulmonary nodules, which can locate small and untouchable lesions in the lung. This method can help surgeons identify lesions more quickly and accurately. It is practical and worthy of promotion.

Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations.

OPINION STATEMENT: The MET exon 14 skipping mutation is found in approximately 3% of lung adenocarcinomas and slightly more than 2% of lung squamous cell carcinomas. In recent years, more and more evidence has shown that MET inhibitors have achieved good anti-tumor effect in patients with MET exon 14 skipping mutation, suggesting that MET exon 14 skipping mutation may be a new target for NSCLC patients. Patients with positive MET exon 14 skipping mutation are recommended to be administered MET inhibitors, and crizotinib is recommended by the NCCN guideline. Due to the presence of gene amplification, second site mutation, bypass activation, and pathological type transformation, one of the inevitable problems of targeted therapy is drug resistance. If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.