scholarly journals Evaluation of Log Odds of Positive Lymph Nodes in Predicting the Survival of Neoadjuvant Therapy Patients with Non-Small Cell Lung Cancer After Surgery: A SEER Cohort-Based Study

Author(s):  
Qing Wang ◽  
Suyu Wang ◽  
Zhiyong Sun ◽  
Min Cao ◽  
Xiaojing Zhao

Abstract Background log odds of positive lymph nodes (LODDS) is a novel lymph node (LN) descriptor, demonstrating promising prognostic value in many tumors. However, there was limited information on LODDS in non-small cell lung cancer (NSCLC) patients, especially those receiving neoadjuvant therapy followed by lung surgery. Methods A total of 2,059 NSCLC patients who received neoadjuvant therapy and surgery were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We used the X-tile software to calculate the cut-off value of LODDS. Kaplan-Meier survival analysis and receiver operating characteristics (ROC) curve were used to compare the predictive value of the American Joint Committee on Cancer (AJCC) N staging descriptor and LODDS. Univariate and multivariate Cox regression and inverse probability of treatment weighting (IPTW) analyses were conducted to construct the model predicting the prognosis. Results LODDS showed better differentiating ability in survival analysis than N staging descriptor (Log-rank test, P<0.0001 vs. P=0.031). The ROC curve demonstrated that the AUC of LODDS was significantly higher than the N staging descriptor in 1-year, 3-year, and 5-year survival analyses (All P<0.05). Univariate and multivariate Cox regression analysis showed that the LODDS was an independent risk factor for NSCLC patients receiving neoadjuvant therapy followed by surgery, both before and after IPTW (all P<0.001). A clinicopathological model with LODDS, age, gender, T, and radiotherapy could better predict the prognosis. Conclusions Compared with the AJCC N staging descriptor, LODDS exhibits better predictive ability for NSCLC patients receiving neoadjuvant therapy followed by surgery. A multivariate clinicopathological model with LODDS included demonstrates sound performance in predicting the prognosis.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wei-Xiao Xue ◽  
Meng-Yu Zhang ◽  
Rui Li ◽  
Xiao Liu ◽  
Yun-Hong Yin ◽  
...  

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.


2021 ◽  
Author(s):  
Huihui Jiang ◽  
Aiqun Xu ◽  
Min Li ◽  
Rui Han ◽  
Enze Wang ◽  
...  

Abstract Background: Non-small cell lung cancer (NSCLC) ranks first among global cancer-related deaths. Despite the emergence of various immunological and targeted therapies, immune tolerance remains a barrier to treatment. Methods: It has been found that this obstacle can be overcome by targeting autophagy-related genes (ATGs). ATGs were screened by coexpression analysis and the genes related to the prognosis of lung cancer were screened using Kaplan–Meier (K-M) survival analysis, univariate Cox regression, and multivariate Cox regression. The prognostic risk model of ATGs was constructed and verified using K-M survival analysis and receiver operating characteristic (ROC) curve analysis. Results: The prognostic risk model of ATGs was constructed. Gene set enrichment analysis (GSEA) showed that the function and pathway of ATG enrichment were closely related to immune cell function. CIBERSORT, LM22 matrix, and Pearson correlation analysis showed that risk signals were significantly correlated with immune cell infiltration and immune checkpoint genes. Conclusions: We identified and independently verified the ATG (AL691432.2, MMP2-AS1, AC124067.2, CRNDE, ABALON, AL161431.1, NKILA) in NSCLC patients and found that immune regulation in the tumor microenvironment is closely related to this gene.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 214s-214s
Author(s):  
C. Hu ◽  
S. Wu ◽  
F. Wu

Introduction: Almost all epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) will develop tyrosine kinase inhibitors (TKIs) resistance. The treatment of oligoprogression is debatable after TKIs resistance. We conducted a real-world retrospective study to evaluate the efficacy of radiotherapy and continuation of TKIs in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. Methods: From January 2011 to January 2018, we retrospectively analyzed EGFR-mutated NSCLC patients with oligoprogression in our institution. 33 patients were treated by radiotherapy and continuation of TKIs. We used Kaplan-Meier and Cox regression model to analyze the prognostic factors of progression-free survival (PFS) and overall survival (OS) from the time of oligoprogression. Variables we selected for analyses included gender, age, smoking status, performance status (PS) score, stage at initial diagnosis, initial resectable, radiotherapy dose, EGFR mutation type, number of metastasis, sites of radiation, T790M status, time of oligometastasis to radiotherapy. Results: 33 patients develop resistance to EGFR TKIs at a median time of 11.0 months. The mPFS and mOS were 6.5 and 21.0 months, respectively. T790M mutation was tested in 8 patients. The mPFS was 11.3 months in T790M mutation positive patients and 6.0 months in negative patients. The mPFS of patients with brain, lung, and bone metastases were 5.7, 6.0, and 13.0 months, respectively. The mPFS in patients who started radiotherapy within or beyond 1 month after oligometastasis was 11.0 months and 5.3 months. The mPFS of patients with postoperative recurrence and initial unresectable were 13.0 and 6.0 months, respectively. Patients with 1 or more than 1 metastatic site showed a mPFS of 11.0 and 4.4 months, respectively. Those who had EGRF exon 21 mutation achieved a mPFS of 11.3 months, whereas those with EGRF exon 19 mutation did worse with a mPFS of 6.5 months. Cox regression model showed no variables significantly correlated with PFS difference. Univariate analysis identified age and smoking status were significantly associated with OS. The results of multivariate analysis indicated that there was no OS-related prognostic factors. Conclusion: Radiotherapy with continued TKIs is an efficacious treatment option in our patients. Age and smoking status were prognostic factors for OS. Our research showed that there was a better survival in patients with T790M mutation, EGRF exon 21 mutation, radiotherapy within 1 month after oligometastasis and bone metastases. However, this was not statistically significant. Prospective studies are needed to validate these clinical results.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2800
Author(s):  
Amir Onn ◽  
Teodor Gottfried ◽  
Amos Stemmer ◽  
Sarit Appel ◽  
Yaacov R. Lawrence ◽  
...  

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.


2020 ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  

Abstract Background: The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrolTM technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods: CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrolTM detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results: The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P < 0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥ 0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions: CTC positive can well predict the recurrence of NSCLC patients. CanPatrolTM technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.


2020 ◽  
Author(s):  
Aisha AL-Dherasi ◽  
Yuwei Liao ◽  
Qi-Tian Huang ◽  
Yichen Wang ◽  
Rulin Hua ◽  
...  

Abstract Background Due to the late and poor prognosis of non-small lung cancer(NSCLC), the mortality of patients is high, underlines the need to identify a credible prognostic marker for NSCLC patients. The aim of our study is to examine the association of allele frequency deviation (AFD) with the patient's survival, as well as identification and validation of a new prognostic signature to predict NSCLC overall survival(OS).Methods First, we developed a new algorithm to calculate AFD from whole-exome sequencing(WES) data, then we compared the predictability of the patient's survival between AFD, tumor mutation burden (TMB) and change of variants allele frequency (dVAF). Second, we overlapped the differentially expressed genes (DEGs) from our data with the genes associated with the survival of The Cancer Genome Atlas (TCGA) database to confirm all genes significantly related to the survival of lung cancer. We identified 149 genes, 31 of which are new genes and have not been reported for lung cancer, that was used to develop a new prognostic model. Lung cancer adenocarcinoma (LUAD) data from the TCGA database was used to validate the gene-signature model. The prognostic model relating to the genes was established and validated in training and LUAD validation groups.Results There was a significant association found between the high AFD value and poor survival among non-small cell lung cancer (NSCLC) patients. A novel seven genes (UCN2, RIMS2, CAVIN2, GRIA1, PKHD1L1, PGM5, CLIC6) were obtained through multivariate Cox regression analysis and significantly associated with NSCLC patients survival. Cox regression analysis confirmed that AFD and 7-gene signature are an independent prognostic marker in NSCLC patients. The AUC for 5-year survival in AFD and the AUC for 3-year survival in both training and validation groups were greater than 0.7.Conclusion As a result, AFD and 7-gene signatures were identified as new independent predictive factors used for predicting the survival among NSCLC patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Qing Ma ◽  
Kai Geng ◽  
Ping Xiao ◽  
Lili Zeng

Background. Non-small-cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. The radiotherapy is one of the most common treatments of NSCLC, and the radiotherapy sensitivity of patients could affect the individual prognosis of NSCLC. However, the prognostic signatures related to radiotherapy response still remain limited. Here, we explored the radiosensitivity-associated genes and constructed the prognostically predictive model of NSCLC cases. Methods. The NSCLC samples with radiotherapy records were obtained from The Cancer Genome Atlas database, and the mRNA expression profiles of NSCLC patients from the GSE30219 and GSE31210 datasets were obtained from the Gene Expression Omnibus database. The Weighted Gene Coexpression Network Analysis (WGCNA), univariate, least absolute shrinkage and selection operator (LASSO), multivariate Cox regression analysis, and nomogram were conducted to identify and validate the radiotherapy sensitivity-related signature. Results. WGCNA revealed that 365 genes were significantly correlated with radiotherapy response. LASSO Cox regression analysis identified 8 genes, including FOLR3, SLC6A11, ALPP, IGFN1, KCNJ12, RPS4XP22, HIST1H2BH, and BLACAT1. The overall survival (OS) of the low-risk group was better than that of the high-risk group separated by the Risk Score based on these 8 genes for the NSCLC patients. Furthermore, the immune infiltration analysis showed that monocytes and activated memory CD4 T cells had different relative proportions in the low-risk group compared with the high-risk group. The Risk Score was correlated with immune checkpoints, including CTLA4, PDL1, LAG3, and TIGIT. Conclusion. We identified 365 genes potentially correlated with the radiotherapy response of NSCLC patients. The Risk Score model based on the identified 8 genes can predict the prognosis of NSCLC patients.


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