Survival Of Non-small Cell Lung Cancer Patients Research Articles

Clinical significance of tumor necrosis and viability in non-small cell lung cancer

BackgroundWe included tumor necrosis (TN) and tumor viability (TV) in our prognostic assessment of patients with non-small cell lung cancer (NSCLC) and investigated their clinical significance.MethodsMedical records of all consecutive subjects who underwent a lobectomy with standard mediastinal lymph node dissection for NSCLC between 2015 to 2016, were reviewed retrospectively. We analyzed the associations of TN and TV with various parameters associated with prognosis as well as survival in NSCLC patients. All analyses were performed regarding neoadjuvant therapy status [the group without neoadjuvant therapy (WON) vs. the group with neoadjuvant therapy (WN)].ResultsA consecutive 154 patients (mean age: 65.0±10.1 years) were included into the present study. Fifteen patients underwent neoadjuvant therapy. Final pathologic stages were IA1 (n=13), IA2 (n=30), IA3 (n=32), IB (n=40), IIA (n=9), IIB (n=18), and IIIA (n=12). WN significantly showed higher TN (P=0.005) and lower TV (P<0.001) than WON. Tumors with vascular, lymphatic, and perineural invasion showed significantly lower TV and higher TN than cases without these features (P=0.014, P=0.019, and P=0.012 for TV; P=0.001, P<0.001, and P<0.001 for TN, respectively). Tumors with poorer differentiation had lower TV (P<0.001) and higher TN (P<0.001) than more differentiated tumors. There was a positive correlation between TN and tumor size (P<0.001) and a negative correlation between TV and tumor size (P=0.031). TN significantly increased as pathologic stage increased (P=0.001), and TV significantly decreased as pathologic stage increased (P=0.038). The group without TN survived significantly longer than the group with TN (P=0.016) in N0 disease and presence of TN and pT stage were independent prognostic factors for survival in N0 disease (P=0.037 and P=0.021, respectively). There was a positive correlation between TN and Ki-67 level (P=0.027). In WN, TN was significantly associated with differentiation (P=0.035), tumor size (P=0.008), and pT stage (P=0.031) but not overall pathologic stage or survival.ConclusionsPresence of histological TN was associated with prognosis of NSCLC, especially in N0 disease, and its usage as a diagnostic or prognostic tool and determination of resection extent could potentially provide prognostic information that can facilitate better management of NSCLC.

55P The impact of liquid next-generation testing timing on treatment-naïve advanced non-small cell lung cancer: A prospective observational study

Liquid next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) has become a promising tool for the identification of driver mutations in non-small cell lung cancer (NSCLC). Whether liquid NGS performed immediately at the start of tumor workup could further enhance NSCLC patient survival is unclear.

Unraveling the mechanism of alkaloids from Sophora alopecuroides Linn combined with immune checkpoint blockade in the treatment of non-small cell lung cancer based on systems pharmacology

Quinolizidine alkaloids, as essential active ingredients extracted from Sophora alopecuroides Linn (SAL), have been proven to be pharmacologically active in a variety of cancers including non-small cell lung cancer (NSCLC). However, whether these alkaloids have substantial benefits in combination with immune checkpoint blockade (ICB) for the treatment of NSCLC is unknown. Here, we explore the potential of these alkaloids in combination with ICB therapy based on a systems pharmacology and bioinformatics approach. We found that 37 alkaloids in SAL have highly similar characteristics in the molecular skeleton, pharmacological properties, and targets. The expression of targets of these alkaloids are significantly correlated with the infiltration level of tumor infiltrating lymphocytes and the expression levels of multiple immune checkpoints in NSCLC. They share similar molecular mechanisms in antitumor immunity. Sophocarpine (Sop) is one of the most representative constituents of these alkaloids. We demonstrated that the Sop promotes PD-L1 expression to improve the effects of PD-L1 blockade treatment via the ADORA1-ATF3 axis. In conclusion, our study identified these alkaloids as promising candidates for the treatment of NSCLC, either alone or in combination with ICB, with potential value for drug development and may provide a promising strategy for improving the survival of NSCLC patients.

Prognostic value of pre-treatment advanced lung cancer inflammation index in non-small cell lung cancer: a meta-analysis

Purpose To identify the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in non-small cell lung cancer (NSCLC) including surgical patients who were diagnosed with early stage. Methods The PubMed, EMBASE and Web of Science electronic databases were searched up to January 12, 2022 for relevant studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between pre-treatment ALI and overall survival (OS) or progression-free survival (PFS) of NSCLC patients. All statistical analyses were conducted by STATA 12.0 software. Results A total of 14 studies involving 3607 participants were included. The pooled results indicated that lower pre-treatment ALI was significantly related to poorer OS (HR = 2.20, 95% CI: 1.46–3.33, P < 0.001) and PFS (HR = 1.78, 95% CI: 1.49–2.13, P < 0.001). Besides, subgroup analysis also demonstrated that lower pre-treatment ALI was associated with worse OS in surgical (P < 0.001) and non-metastatic (P < 0.001) patients and worse PFS of surgical (P < 0.001) NSCLC patients. Conclusion Pre-treatment ALI was a novel and reliable prognostic indicator in NSCLC and lower pre-treatment ALI predicted worse survival including patients diagnosed with early stage. However, more prospective high-quality studies are still needed to verify the above findings.

Elevated air quality index and fine particulate matter levels contribute to the poor prognosis and progression of nonsmall-cell lung cancer: A cohort study combined with external validation.

BackgroundPoor air quality can result in a variety of respiratory disorders. However, the air quality index (AQI) and the level of fine particulate matter (PM2.5) on the progression and prognosis of nonsmall‐cell lung cancer (NSCLC) are unclear.MethodsWe launched a cohort study focused on the relationship between air quality and overall survival as well as progression, incorporating data from 590 patients with NSCLC in our medical center between November 1, 2013 and March 1, 2016. Forty‐nine patients from Sichuan Cancer Hospital were used for validation.ResultsCases with poorer AQI 6 months before NSCLC diagnosis were more likely to progress to stage III to IV NSCLC than controls (OR = 2.61, 95% CI 1.35–5.24, p = 0.005). Similarly, if exposed to high levels of PM2.5 during these 6 months, overall survival was poor (HR [95% CI] = 1.53 [1.13, 2.07], p = 0.006). According to multivariate analysis, age, gender, KPS, PM2.5, hyperlipemia, and NSCLC stage were independent risk factors of overall survival. A predictive model developed by these factors above yielded a favorable agreement (C‐index = 0.758) on the calibration curve. External validation was conducted by 46 patients from Sichuan Cancer Hospital displaying an AUC of 0.724 (0.684–0.763).ConclusionsPM2.5 and AQI levels affect disease progression and long‐term survival in NSCLC patients. An overall survival prediction model based on the PM2.5 level can help clinicians predict the risk of death in NSCLC.

Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study.

Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700mg defined low (LCD) or high (HCD) cumulative dosing during the 90days before starting ICIs. At least one 5-day course of ≥ 10mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5days) or continuous (CCD, > 5days). We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1-2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6months (95%CI: 3.9-6.3) and median OS was 6.9months (95% CI: 6.0-8.9) after a median follow-up time of 43.5months (95% CI: 32.6-54.4). Multivariate analysis of survival confirmed ECOG PS 1-2 (p = 0.005), negative PD-L1 expression (p = 0.002), and CCD (p = 0.001) significantly correlated with an increased risk of mortality. These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results.

The association between proton pump inhibitor use and systemic anti-tumour therapy on survival outcomes in patients with advanced non-small cell lung cancer: A systematic review and meta-analysis.

Proton pump inhibitors (PPIs) are often prescribed to prevent or treat gastrointestinal disease. Whether the combination of systemic anti-tumour therapy and PPIs leads to poor outcomes in patients with advanced non-small cell lung cancer (NSCLC) is unclear. This systematic review explored the relationship between PPIs and survival outcomes of patients with advanced NSCLC who are receiving systemic anti-tumour therapy. We searched studies reporting the overall survival (OS) and/or progression-free survival (PFS) of advanced NSCLC patients who are receiving systemic anti-tumour therapy with or without PPIs on PubMed, EMBASE and the Cochrane Library for literature published prior to 31 August 2021. The meta-analysis used a random effects model to estimate the hazard ratio (HR) with 95% confidence intervals (CI) and I2 to assess statistical heterogeneity. Publication bias and sensitivity analysis were performed. Fourteen retrospective studies comprising 13 709 advanced NSCLC patients were identified. Subgroup analyses showed that the use of PPI was correlated with the OS or PFS of patients receiving chemotherapy, targeted therapy, and immunotherapy (PPI users' group vs non-users' group: HR for OS = 1.35, 95% CI = 1.21-1.51, P < .00001; HR for PFS = 1.50, 95% CI = 1.25-1.80, P < .0001). Publication bias and sensitivity analyses confirmed that the results were robust. Meta-analysis demonstrated that PPI use in advanced NSCLC patients who were undergoing systemic anti-tumour therapy was correlated with increased mortality risk. Until results are further confirmed, caution should be applied when administering PPIs and systemic anti-tumour therapy to advanced NSCLC patients.

PLA2G10 incorporated in exosomes could be diagnostic and prognostic biomarker for non-small cell lung cancer

BackgroundExosomal cargos such as nucleic acids and proteins have been attracting major interest as promising diagnostic biomarkers of cancers. The aim of this study was to characterize the mRNA profiles of serum exosomes and to identify non-small cell lung cancer (NSCLC) related mRNAs with higher sensitivity and specificity to diagnose and predict prognosis of NSCLC. MethodsmRNA microarray analysis was conducted to screen differentially expressed mRNAs in the serum exosomes of NSCLC patients. Selected exosomal mRNA candidate PLA2G10 and PLA2G10 protein were quantified by RT-qPCR and ELISA assay, respectively, in the sample cohorts of healthy, benign lung tumor and NSCLC. Receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic power of exosomal PLA2G10 mRNA and protein. Kaplan-Meier plots were used to estimate patients’ overall and disease-free survival. ResultsSerum exosomal PLA2G10 mRNA levels were elevated in NSCLC patients, and were closely related to more aggressive characteristics (higher stages, lymphatic node metastasis and distant metastasis) and poor overall and disease-free survival of NSCLC patients. Intriguingly, PLA2G10 protein was proved to be incorporated in exosomes, and its expression patterns and relationship with clinical pathological factors were similar to exosomal PLA2G10 mRNA. Additionally, the levels of exosomal PLA2G10 mRNA and protein were positively correlated and their combination could improve the diagnostic power to discriminate less and more malignance of NSCLC. ConclusionsIncreased levels of serum exosomal PLA2G10 mRNA and protein were associated with more aggressive features of NSCLC, suggesting their potential as diagnostic and prognostic biomarkers of NSCLC.

Impact of the examined number of lymph nodes at N1 station on the prognosis of patients with pT1-3N0M0 non-small cell lung cancer

Objective: To investigate the relationship between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC). Methods: A total of 337 patients with pT1-3N0M0 NSCLC who underwent radical lung cancer surgery at the Provincial Hospital Affiliated to Anhui Medical University from January 2013 to March 2015 were selected. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for predicting 5-year survival in pT1-3N0M0 NSCLC patients by the examined number of lymph nodes at the N1 station. The relationships between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 NSCLC were analyzed according to the optimal cut-off group. Results: A total of 1 321 lymph nodes at N1 station were examined in 337 patients, with a mean of 3.9 nodes per patient. The median survival time was 42.0 months, with 1-, 3- and 5-year survival rates of 82.2%, 57.1% and 24.9%, respectively. ROC curve analysis showed that the optimal cut-off value of 4.5 lymph nodes examined at the N1 station was used to predict 5-year survival in patients with pT1-3N0M0 NSCLC. After rounding off the number, the number of lymph nodes examined at the N1 station was 5 as the cut-off value, and the patients were divided into the group with <5 lymph nodes examined (212 cases) and the group with ≥5 lymph nodes examined (125 cases). The proportion of patients received adjuvant chemotherapy was 19.2% in the group with ≥5 lymph nodes examined, which was higher than 9.0% in the group with <5 lymph nodes examined (P=0.007), and the differences in other clinicopathological characteristics between the two groups were not statistically significant (P>0.05). The median survival time for patients in the group with <5 lymph nodes examined was 38.0 months, with 1-, 3- and 5-year survival rates of 80.1%, 52.5% and 15.6%, respectively. The median survival time for patients in the group with ≥5 lymph nodes examined was 48.0 months, and the 1-, 3- and 5-year survival rates were 85.6%, 64.0% and 36.0%, respectively. The survival rate of patients in the group with ≥5 lymph nodes examined was better than that in the group with <5 lymph nodes examined (P=0.002). Multifactorial Cox regression analysis showed that T stage (OR=1.408, 95% CI: 1.118-1.670) and the examined number of lymph nodes at N1 station (OR=0.670, 95% CI: 0.526-0.853) were independent influence factors for the prognosis of pT1-3N0M0 NSCLC patients. Conclusion: The examined number of lymph nodes at the N1 station is associated with the prognosis of patients with pT1-3N0M0 NSCLC, and the examination of at least 5 lymph nodes at N1 station at the time of postoperative pathological examination improves the 5-year survival rate of patients.

A novel LASSO‐derived prognostic model predicting survival for non‐small cell lung cancer patients with M1a diseases

IntroductionThe current American Joint Committee on Cancer (AJCC) M1a staging of non‐small cell lung cancer (NSCLC) encompasses a wide disease spectrum, showing diverse prognosis.MethodsPatients who diagnosed in an earlier period formed the training cohort, and those who diagnosed thereafter formed the validation cohort. Kaplan–Meier analysis was performed for the training cohort by dividing the M1a stage into three subgroups: (I) malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE); (II) separate tumor nodules in contralateral lung (STCL); and (III) pleural tumor nodules on the ipsilateral lung (PTIL). Gender, age, histologic, N stage, grade, surgery for primary site, lymphadenectomy, M1a groups, and chemotherapy were selected as independent prognostic factors using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. And a nomogram was constructed using Cox hazard regression analysis. Accuracy and clinical practicability were separately tested by Harrell's concordance index, the receiver operating characteristic (ROC) curve, calibration plots, residual plot, the integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).ResultsThe concordance index (0.661 for the training cohort and 0.688 for the validation cohort) and the area under the ROC curve (training cohort: 0.709 for 1‐year and 0.727 for 2‐year OS prediction; validation cohort: 0.737 for 1‐year and 0.734 for 2‐year OS prediction) indicated satisfactory discriminative ability of the nomogram. Calibration curve and DCA presented great prognostic accuracy, and clinical applicability. Its prognostic accuracy preceded the AJCC staging with evaluated NRI (1‐year: 0.327; 2‐year: 0.302) and IDI (1‐year: 0.138; 2‐year: 0.130).ConclusionOur study established a nomogram for the prediction of 1‐ and 2‐year OS in patients with NSCLC diagnosed with stage M1a, facilitating healthcare workers to accurately evaluate the individual survival of M1a NSCLC patients. The accuracy and clinical applicability of this nomogram were validated.

Potentials of Non-Invasive 18F-FDG PET/CT in Immunotherapy Prediction for Non-Small Cell Lung Cancer.

The immune checkpoint inhibitors (ICIs), by targeting cytotoxic-T-lymphocyte-associated protein 4, programmed cell death 1 (PD-1), or PD-ligand 1, have dramatically changed the natural history of several cancers, including non–small cell lung cancer (NSCLC). There are unusual response manifestations (such as pseudo-progression, hyper-progression, and immune-related adverse events) observed in patients with ICIs because of the unique mechanisms of these agents. These specific situations challenge response and prognostic assessment to ICIs challenging. This review demonstrates how 18F-FDG PET/CT can help identify these unusual response patterns in a non-invasive and effective way. Then, a series of semi-quantitative parameters derived from 18F-FDG PET/CT are introduced. These indexes have been recognized as the non-invasive biomarkers to predicting the efficacy of ICIs and survival of NSCLC patients according to the latest clinical studies. Moreover, the current situation regarding the functional criteria based on 18F-FDG PET/CT for immunotherapeutic response assessment is presented and analyzed. Although the criteria based on 18F-FDG PET/CT proposed some resolutions to overcome limitations of morphologic criteria in the assessment of tumor response to ICIs, further researches should be performed to validate and improve these assessing systems. Then, the last part in this review displays the present status and a perspective of novel specific PET probes targeting key molecules relevant to immunotherapy in prediction and response assessment.

Long non-coding RNA LINRIS is upregulated in non-small cell lung cancer and its silencing inhibits cell proliferation by suppressing microRNA-10a maturation

ABSTRACT Long noncoding RNA LINRIS (LINC00920) is known to participate in colorectal cancer. This study aimed to explore the role of LINRIS in non-small cell lung cancer (NSCLC). NSCLC and adjacent non-tumor tissues were collected from 62 NSCLC patients. LINRIS expression was detected using real-time quantitative PCR (RT-qPCRs). The 62 NSCLC patients were monitored every month for 5 years to evaluate the role of LINRIS in predicting the prognosis of NSCLC. The effects of LINRIS silencing on microRNA-10a (miR-10a) precursor and mature miR-10a levels were assessed by RT-qPCR. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) assays. LINRIS expression was upregulated in NSCLC tissues. High LINRIS levels predicted poor survival of NSCLC patients. LINRIS were positively correlated with mature (miR-10a) levels but not miR-10a precursor. In NSCLC cells, LINRIS silencing showed no role in miR-10a precursor accumulation but downregulated mature miR10a level. Moreover, LINRIS silencing inhibited cell proliferation, while miR-10a overexpression increased cell proliferation and inhibited the role of LINRIS silencing. Overall, LINRIS silencing may inhibit NSCLC cell proliferation by suppressing miR-10a maturation. Abbreviations: Non-small cell lung cancer (NSCLC); Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR); LncRNA long intergenic noncoding RNA for IGF2BP2 stability (LINRIS).

Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis.

Background The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, P < 0.001; I2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, P < 0.001; I2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, P=0.003; HR for OS: 1.43, P=0.001). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Conclusions Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.

LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in NSCLC through stabilizing TDP43 and EIF2S1

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective targeted therapy drugs for advanced non-small cell lung cancer (NSCLC) patients carrying sensitized EGFR mutations. The rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing NSCLC. The chromosome 4q12 is the first genome-wide association study (GWAS)-reported locus associated with progression-free survival (PFS) of NSCLC patients treated with EGFR-TKIs. However, the biological significance of the noncoding transcripts at 4q12 in NSCLC remains elusive. In the present study, we identified two 4q12 long noncoding RNAs (lncRNAs) LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs efficiency. In line with their oncogenic role, evidently higher LCETRL3 and LCETRL4 levels were observed in NSCLC tissues as compared with normal specimens. Importantly, lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of TDP43. Similarly, lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of EIF2S1. In particular, elevated levels of LCETRL3 or LCETRL4 in NSCLC cells resulted in stabilization of TDP43 or EIF2S1, increased levels of NOTCH1 or phosphorylated PDK1, activated AKT signaling and, thus, EGFR-TKIs resistance. Taken together, our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in NSCLC. These findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets, i.e., lncRNAs, which may unlock the therapeutic potential of EGFR-TKIs resistant NSCLC in the clinic.

Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression

Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. In addition to coding genes, the contribution of long noncoding RNA (lncRNA) to non-small cell lung cancer (NSCLC) remains unclear. Here, we explored lncRNA expression profiles by Affymetrix Gene Chip Human Transcriptome Array 2.0 in 37 paired samples of tumorous NSCLC tissues and adjacent nontumorous tissues. We showed that LHFPL3-AS2 is a novel lncRNA, significantly decreased in NSCLC tissues. LHFPL3-AS2 was further validated in an additional 93 paired samples of NSCLC. Low levels of LHFPL3-AS2 expression were highly correlated with poor overall survival, TNM stage, and metastasis of NSCLC patients. Enhanced expression of LHFPL3-AS2 inhibited NSCLC invasion and metastasis in vitro and in vivo. Moreover, downregulation of LHFPL3-AS2 reduced its specific interaction with SFPQ, resulting in more SFPQ binding to the promoter of TXNIP and causing the transcriptional repression of TXNIP, thus finally promoting the migration and invasion of NSCLC cells. Furthermore, LHFPL3-AS2 was shown to be regulated by EGR1 under hypoxia.

Effect of Adjuvant Chemotherapy on Survival of Patients With 8th Edition Stage IB Non-Small Cell Lung Cancer.

BackgroundThe efficacy of adjuvant chemotherapy in patients with 8th edition stage IB (tumor size ≤4 cm) non-small cell lung cancer (NSCLC) remains unclear.MethodsWe identified 9757 eligible patients (non-chemotherapy group: n=8303; chemotherapy group: n=1454) between 2004 and 2016 from the Surveillance, Epidemiology and End Results (SEER) database. Log-rank test was used to compare overall survival (OS) between the chemotherapy and non-chemotherapy groups. Cox regression model was applied to investigate the independent prognosis factors of all surgically treated stage IB patients, and then the nomogram was constructed. Propensity score matching (PSM) was performed to reduce the confounding bias, and subgroup analyses of the matched cohort were also performed. Finally, we reviewed 184 patients with stage IB NSCLC from July 2008 to December 2016 in Jinling Hospital as a validation cohort, and compared disease-free survival (DFS) and OS between the two groups.ResultsIn the SEER database cohort, adjuvant chemotherapy was associated with improved OS in both unmatched and matched (1417 pairs) cohorts (all P <0.05). The survival benefit (both OS and DFS) was confirmed in the validation cohort (P <0.05). Multivariate analysis showed age, race, sex, marital status, histology, tumor location, tumor size, differentiation, surgical method, lymph nodes (LNs) examined, radiotherapy and chemotherapy were prognostic factors for resected stage IB NSCLC (all P <0.05). The concordance index and calibration curves demonstrated good prediction effect. Subgroup analyses showed patients with the following characteristics benefited from chemotherapy: old age, poor differentiation to undifferentiation, 0-15 LNs examined, visceral pleural invasion (VPI), lobectomy and no radiotherapy (all P <0.05).ConclusionsAdjuvant chemotherapy is associated with improved survival in 8th edition stage IB NSCLC patients, especially in those with old age, poorly differentiated to undifferentiated tumors, 0-15 LNs examined, VPI, lobotomy and no radiotherapy. Further prospective trials are needed to confirm these conclusions. Besides, the nomogram provides relatively accurate prediction for the prognosis of resected stage IB NSCLC patients.

Local consolidative therapy for synchronous oligometastatic non-small cell lung cancer treated with first-line pembrolizumab: A retrospective observational study.

BackgroundLocal consolidative therapy (LCT) has emerged as a treatment option in patients with oligometastatic non‐small cell lung cancer (NSCLC) undergoing chemotherapy or targeted therapy. However, the current literature lacks evidence as to whether LCT improves survival in NSCLC patients receiving immunotherapy. Our study aimed to assess whether LCT combined with pembrolizumab ± chemotherapy could improve the survival of patients with synchronous oligometastatic NSCLC.MethodsPatients with NSCLC, without EGFR or ALK genetic aberrations, who were treated with first‐line pembrolizumab ± chemotherapy, were included in the study. Survival analysis of the LCT and non‐LCT groups was compared.ResultsA total of 231 patients were included in the study. The median follow‐up time was 15.24 months. Median progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 12.00 and 23.43 months, respectively. Of the 231 patients included, 76 patients received LCT combined with pembrolizumab ± chemotherapy (LCT group) while 155 patients received pembrolizumab ± chemotherapy alone (non‐LCT group). Of note, the PFS of the LCT and non‐LCT groups was 13.97 and 10.08 months (p = 0.016), respectively. The OS were 30.67 and 21.97 months (p = 0.011), respectively. The PFS and OS were significantly improved with LCT for patients with brain or lung metastases but not bone metastases. No significant increase in treatment‐related toxicity was observed in the LCT group.ConclusionsThe present study shows that LCT to metastatic sites is an option for consideration in patients with synchronous oligometastatic NSCLC during first‐line pembrolizumab treatment, with significantly improved PFS and OS compared with systemic treatment alone.

Machine Learning Using Real-World and Translational Data to Improve Treatment Selection for NSCLC Patients Treated with Immunotherapy.

Simple SummaryIn this paper, the authors show that artificial intelligence (AI) and machine learning (ML) are useful approaches to integrate multifactorial data and helpful for personalized prediction. In detail, compared to PD-L1 for advanced non-small cell lung cancer (NSCLC), ML tools predicted better responder (R) and non-responder (NR) patients to immunotherapy (IO). It was also able to indirectly foresee OS and PFS of R and NR patients. Given the high incidence of NSCLC, and the absence of reliable biomarkers to predict the response to IO other than PD-L1, the authors believe this research may be of great interest to anyone involved in thoracic oncology. Furthermore, given the growing interest from the scientific community in AI and ML, the authors believe that this manuscript could represent a fascinating topic to anyone who needs to exploit the enormous potential of these tools in the treatment of cancer.(1) Background: In advanced non-small cell lung cancer (aNSCLC), programmed death ligand 1 (PD-L1) remains the only biomarker for candidate patients to immunotherapy (IO). This study aimed at using artificial intelligence (AI) and machine learning (ML) tools to improve response and efficacy predictions in aNSCLC patients treated with IO. (2) Methods: Real world data and the blood microRNA signature classifier (MSC) were used. Patients were divided into responders (R) and non-responders (NR) to determine if the overall survival of the patients was likely to be shorter or longer than 24 months from baseline IO. (3) Results: One-hundred sixty-four out of 200 patients (i.e., only those ones with PD-L1 data available) were considered in the model, 73 (44.5%) were R and 91 (55.5%) NR. Overall, the best model was the linear regression (RL) and included 5 features. The model predicting R/NR of patients achieved accuracy ACC = 0.756, F1 score F1 = 0.722, and area under the ROC curve AUC = 0.82. LR was also the best-performing model in predicting patients with long survival (24 months OS), achieving ACC = 0.839, F1 = 0.908, and AUC = 0.87. (4) Conclusions: The results suggest that the integration of multifactorial data provided by ML techniques is a useful tool to select NSCLC patients as candidates for IO.

Retrospective analysis of long‐term survival factors in patients with advanced non‐small cell lung cancer treated with nivolumab

BackgroundNivolumab, an immune checkpoint inhibitor (ICI), has changed the treatment paradigm for advanced non‐small cell lung cancer (NSCLC). However, factors associated with long‐term survival in NSCLC patients treated with ICIs remain unknown. This study aimed to evaluate patient characteristics and clinical laboratory changes related to long‐term survival in NSCLC patients treated with nivolumab, using real‐world data.MethodsWe retrospectively reviewed the medical records of consecutive patients with advanced NSCLC with Eastern Cooperative Oncology Group performance status (ECOG‐PS) ≤1 treated with nivolumab. We defined patients with overall survival (OS) ≥3 years as long‐term survivors. We evaluated the differences in patient characteristics and tumor response between nonlong‐term survivors and long‐term survivors and performed univariate and multivariate analyses of factors associated with long‐term survival.ResultsOut of 213 patients with advanced NSCLC treated with nivolumab, 162 patients with ECOG‐PS ≤1 were included in the study. Young age, ECOG‐PS 0, absolute neutrophil count decrease, lymphocyte percentage increase, and neutrophil‐to‐lymphocyte ratio (NLR) change (ΔNLR) <1 were significantly associated with long‐term survival. Long‐term survivors had significantly higher response and disease control rates than nonlong‐term survivors. Multivariate analysis showed that ΔNLR <1 was significantly associated with long‐term survival. Further, OS was significantly different between the PS 0 and PS 1 groups (median OS: 32.0 months vs. 10.6 months) and the nonincreasing NLR and increasing NLR groups (median OS: 20.8 months vs. 5.7 months).ConclusionsΔNLR <1 was a significant long‐term survival factor compared to ΔNLR ≥1 in advanced NSCLC patients treated with nivolumab.

Advances in Targeted Therapy Against Driver Mutations and Epigenetic Alterations in Non-Small Cell Lung Cancer

The incidence and mortality of lung cancer rank top three of all cancers worldwide. Accounting for 85% of the total number of lung cancer, non-small cell lung cancer (NSCLC) is an important factor endangering human health. Recently, targeted therapies against driver mutations and epigenetic alterations have made encouraging advances that benefit NSCLC patients. Druggable driver mutations, which mainly occur in EGFR, KRAS, MET, HER2, ALK, ROS1, RET and BRAF, have been identified in more than a quarter of NSCLC patients. A series of highly selective mutant targeting inhibitors, such as EGFR tyrosine kinase inhibitors and KRAS inhibitors, have been well studied and applied in clinical treatments, which greatly promote the overall survival of NSCLC patients. However, drug resistance has become a major challenge for targeted treatment, and a variety of methods to overcome drug resistance are constantly being developed, including inhibitors against new mutants, combination therapy with other pathway inhibitors, etc. In addition, epigenetics-based therapy is emerging. Epigenetic regulators such as histone deacetylases and non-coding RNA play a crucial role in the development of cancer and drug resistance by affecting multiple signaling pathways. Epigenetics-based therapeutic strategies combined with targeted drugs show great clinical potential. Many agents targeting epigenetic changes are being investigated in preclinical studies, with some already under clinical trials. This article focuses on driver mutations and epigenetic alterations in association with relevant epidemiological data. We introduce the current status of targeted inhibitors and known drug resistance, review advances in major targeted therapies with recent data from preclinical and clinical trials, and discuss the possibility of combination therapy against driver mutations and epigenetic alterations in overcoming drug resistance.