Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.

BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can't meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. METHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. RESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. CONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

[Analysis of the Effcacy and Safety of Amivantamab in Non-small Cell Lung Cancer 
Patients with EGFR/MET Gene Abnormalities: A Single Center's Experience].

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS: Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.

Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT-qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

The prevalence and real-world therapeutic analysis of Chinese patients with KRAS-Mutant Non-Small Cell lung cancer.

OBJECTIVE: Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important driver gene of non-small cell lung cancer (NSCLC). Despite a rapid progress achieved in the targeted therapy, chemotherapy remains the standard treatment option for patients with KRAS-mutant NSCLC. This study aimed to assess real-world data of Chinese patients with KRAS-mutant NSCLC undergoing chemotherapy and/or immunotherapy. METHODS: KRAS mutational status was analyzed using next-generation sequencing of 150,327 NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I). Treatment data were collected and analyzed retrospectively from 4348 NSCLC patients who were admitted to the Peking University Cancer Hospital and Institute between January 2009 and October 2020 (Cohort II). RESULTS: In Cohort I, 18,224 patients were detected with KRAS mutations (12.1%) of whom G12C (29.6%) was the most frequent subtype, followed by G12D (18.1%) and G12V (17.5%). In case of concomitant mutations, TP53 had the highest incidence of 33.6%, followed by EGFR (11.6%), STK11 (10.4%), KEAP1(6.2%), and CDKN2A (6.0%). Cohort II included 497 patients (11.4%) with KRAS mutations. In the first-line chemotherapeutic analysis of Cohort II, patients benefited more from the pemetrexed/platinum (PP) regimen than the gemcitabine/platinum (GP) or taxanes/platinum (TP) regimen (median progression-free survival [PFS], 6.4 vs. 4.9 vs. 5.6 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.48-0.88, p = 0.033 and HR = 0.69, 95% CI 0.47-1.00, p = 0.05, respectively), with no significant difference when combined with bevacizumab. Regarding patients who received immune checkpoint inhibitors (ICIs), the objective response rate was 26% for a median PFS of 9.6 months (95% CI 6.16-13.03). Patients who received ICIs combined with chemotherapy had a significantly longer survival than monotherapy (median PFS, 13.9 vs. 5.2 months, HR = 0.59, 95% CI 0.35-0.99, p = 0.049). CONCLUSION: KRAS is an important driver gene in NSCLC, compromising 12.1% in this study, and G12C was noted as the most common subtype. Patients with KRAS-mutant NSCLC could benefit from pemetrexed-based chemotherapy and ICIs.

[Advances in Immunotherapy for Malignant Pleural Mesothelioma].

Patients with malignant pleural mesothelioma (MPM) usually present with poor prognosis and short survival period, and there has been a lack of effective treatment options for a long time. Chemotherapy has limited improvement in the clinical outcome of advanced patients (the median survival is less than one year), and it is difficult to find suitable targets for targeted therapy. Recent in-depth research on immunotherapy has changed the treatment pattern of MPM. Especially, the dual immunotherapy regimen significantly improved the survival outcome of patients across subgroups and prolonged the survival time of MPM patients. Therefore, it has been approved for unresectable MPM as first-line treatment for patients. The exploration of other mono or combo immunotherapy regimens in the first and second-line settings of MPM is also underway. How to identify the best beneficial population of each regimen through predictive biomarkers is also a hot spot for researchers. This article will focus on the most up-to-date progress of MPM epidemiology, histological characteristics, pathogenesis, treatment patterns and the advances of immunotherapy in the disease.
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Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy.

BACKGROUND: For advanced nonsquamous non-small cell lung cancer (NSCLC), the mechanisms of resistance to first-line immunotherapy are not clear. Immune checkpoint inhibitors (ICIs) in combination with agents targeting other pathways may serve as second-line therapy options. Apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) could increase the efficacy of camrelizumab (an ICI agent). The efficacy and safety of this combination regimen as a second-line therapy for NSCLC patients after failure on first-line immunotherapy has not previously been evaluated. METHODS: In this single-arm, multicenter, phase II trial, metastatic nonsquamous NSCLC patients previously treated with single-agent ICI or ICI plus chemotherapy will be enrolled. Participants will receive intravenous camrelizumab 200 mg D1 and oral apatinib 250 mg D1-21 for a 21-day cycle. The study treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression-free survival by investigator. Secondary endpoints are overall survival, objective response rate, disease control rate, duration of response by investigator, quality of life, safety, and toxicity. CONCLUSIONS: This trial will provide evidence of the benefit of treatment with camrelizumab combined with apatinib in advanced nonsquamous NSCLC patients who were previously treated with first-line immunotherapy.

Evaluation of different treatment strategies between right-sided and left-sided pneumonectomy for stage I-IIIA non-small cell lung cancer patients.

BACKGROUND: This study aimed to assess the different survival outcomes of stage I-IIIA non-small cell lung cancer (NSCLC) patients who received right-sided and left-sided pneumonectomy, and to further develop the most appropriate treatment strategies. METHODS: We accessed data from the Surveillance, Epidemiology, and End Results database from the United States for the present study. An innovative propensity score matching analysis was used to minimize the variance between groups. RESULTS: For 2,683 patients who received pneumonectomy, cancer-specific survival [hazard ratio (HR) =0.863, 95% confidence interval (CI): 0.771 to 0.965, P=0.010] and overall survival (OS; HR =0.875, 95% CI: 0.793 to 0.967, P=0.008) were significantly superior in left-sided pneumonectomy patients compared with right-sided pneumonectomy patients. Cancer-specific survival (HR =0.847, 95% CI: 0.745 to 0.963, P=0.011) and OS (HR =0.858, 95% CI: 0.768 to 0.959, P=0.007) were also significantly longer with left-sided compared to right-sided pneumonectomy after matching analysis of 2,050 patients. Adjuvant therapy could significantly prolong cancer-specific survival (67 versus 51 months, HR =1.314, 95% CI: 1.093 to 1.579, P=0.004) and OS (46 versus 30 months, HR =1.458, 95% CI: 1.239 to 1.715, P<0.001) among left-sided pneumonectomy patients after the matching procedure, while adjuvant therapy did not increase cancer-specific survival for right-sided pneumonectomy patients (46 versus 42 months, HR =1.112, 95% CI: 0.933 to 1.325, P=0.236). Subgroup analysis showed that adjuvant chemotherapy could significantly improve cancer-specific survival and OS for all pneumonectomy patients. However, radiotherapy was associated with worse survival for patients with right-sided pneumonectomy. CONCLUSIONS: Pneumonectomy side can be deemed as an important factor when physicians determine the most optimal treatment strategies.

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting.

BACKGROUND: Pemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting. METHODS: The response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up. RESULTS: Of 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event. CONCLUSIONS: Pemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.

Identification of serum biomarkers to predict pemetrexed/platinum chemotherapy efficacy for advanced lung adenocarcinoma patients by data-independent acquisition (DIA) mass spectrometry analysis with parallel reaction monitoring (PRM) verification.

BACKGROUND: Pemetrexed/platinum chemotherapy has been the standard chemotherapy regimen for lung adenocarcinoma patients, but the efficacy varies considerably. METHODS: To discover new serum biomarkers to predict the efficacy of pemetrexed/platinum chemotherapy, we analyzed 20 serum samples from advanced lung adenocarcinoma patients who received pemetrexed/platinum chemotherapy with the data-independent acquisition (DIA) quantitative mass spectrometry (MS). RESULTS: The 20 patients were categorized as "good response" [12 patients achieving partial response (PR)] and "poor response" [8 patients with progressive disease (PD)] groups. Altogether 23 significantly different expressed proteins were identified, which had relative ratios higher than 1.2 or lower than -0.83, with 7 proteins having an area under the curve (AUC) above 0.8. To further validate the DIA results, we used the parallel reaction monitoring (PRM) method to examine 16 candidate serum biomarkers in the study cohort of 20 patients and another cohort of 22 advanced lung adenocarcinoma patients (16 PR and 6 PD). Quantitative validation using PRM correlated well with the DIA results, and 10 promising proteins exhibited a similar up- or downregulation. It is worth noting that glutathione peroxidase 3 (GPX3) exhibits significant upregulation in the poor response group compared with the good response group, which was validated by both DIA and PRM methods. CONCLUSIONS: Our study confirmed that combined DIA MS and PRM approaches were effective in identifying serum predictive biomarkers for advanced lung adenocarcinoma patients. Further studies are needed to explore the potential biological mechanism underlying these biomarkers.

Plasma cytokines interleukin-18 and C-X-C motif chemokine ligand 10 are indicative of the anti-programmed cell death protein-1 treatment response in lung cancer patients.

BACKGROUND: Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first- and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment. METHODS: We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition. RESULTS: The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs. CONCLUSIONS: Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.

Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients.

BACKGROUND: Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. METHODS: This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. RESULTS: Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P < 0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs. 25.0%, P = 0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. CONCLUSIONS: Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.

Nomogram model for predicting cause-specific mortality in patients with stage I small-cell lung cancer: a competing risk analysis.

BACKGROUND: The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes. METHODS: The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients. RESULTS: 1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate. CONCLUSIONS: We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.

The adverse events associated with combination immunotherapy in cancers: Challenges and chances.

With the development of cancer immunotherapy, the combination strategy is becoming prevalent. Multiple relevant clinical trials are ongoing in this field. However, immune-related adverse events (irAEs) occurred more frequently, showing a different pattern from single-agent therapy. It is necessary for clinicians to learn about the characteristics of AEs from combination immunotherapy, and master the skills to deal with them. In this article, we reviewed presently published data about AEs from combination immunotherapy of cancers. We believe a full-scale view about this new treatment strategy will facilitate oncologists to better understand tumor immune response. With cutting edge knowledge, an experienced team can minimize these AEs and help patients to achieve high-quality long-term survival.

A nomogram model to predict death rate among non-small cell lung cancer (NSCLC) patients with surgery in surveillance, epidemiology, and end results (SEER) database.

BACKGROUND: This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery.. METHODS: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCLC patients who received surgery. RESULTS: A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P < 0.001). Patients who received chemotherapy and radiotherapy had significant higher lung cancer related death rate but were associated with significant lower non-cancer related mortality (P<0.001). A nomogram model was established based on multivariate models of training data set. In the validation cohort, the unadjusted C-index was 0.73 (95% CI, 0.72-0.74), 0.71 (95% CI, 0.66-0.75) and 0.69 (95% CI, 0.68-0.70) for lung cancer related death, other cancer related death and non-cancer related death. CONCLUSIONS: A prognostic nomogram model was constructed to give information about the risk of death for NSCLC patients who received surgery.

Effects of Surgery on Survival of Early-Stage Patients With SCLC: Propensity Score Analysis and Nomogram Construction in SEER Database.

Purpose: We aimed to assess the survival benefit of surgery for patients with stage IA-IIB small cell lung cancer (SCLC) and construct a nomogram for predicting overall survival (OS). Methods: Patients who had been diagnosed with stage IA-IIB SCLC between 2004 and 2014 and who had received active treatment were selected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was OS. Cox proportional hazards models and propensity score (PS) analyses were used to compare the associations between surgery and OS. The probability of 1- and 3-year OS was predicted using a nomogram. Results: We reviewed 2,246 patients. The median OS of the surgery and non-surgery groups was 35 months and 19 months, respectively. Multivariable Cox proportional hazards models showed a survival benefit in the surgery group (hazards ratio [HR], 0.642; 95% confidence interval [CI], 0.557-0.740; P < 0.001). To balance the between-group measurable confounders, the impact of surgery on OS was assessed using PS matching. After PS matching, OS analysis still favored surgical resection. The PS-stratification, PS-weighting, and PS-adjustment models showed similar results to demonstrate a statistically significant benefit for surgery. Further, the nomogram was well calibrated and had good discriminative ability (Harrell's C-index = 0.645). Conclusion: Our analysis suggests that surgery is a viable option for patients with early-stage SCLC. Our nomogram is a viable tool for quantifying treatment trade-off assumptions and may assist clinicians in decision-making. Future work is needed to validate our results and improve our tools.

Retrospective analysis of the effectiveness and tolerability of nab-paclitaxel in Chinese elderly patients with advanced non-small-cell lung carcinoma.

BACKGROUND: Previous trials have suggested that elderly patients with non-small-cell lung cancer (NSCLC) could benefit from nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Real-world data on the elderly Chinese population are lacking. This study aimed to analyze the effectiveness and tolerability of nab-paclitaxel in Chinese elderly patients (≥65 years) with advanced NSCLC. METHODS: This study included 76 patients with a primary diagnosis of IIIB-IV NSCLC from January 2010 to December 2017 at Peking University Cancer Hospital, who received nab-paclitaxel (125 or 130 mg/m2 i.v.) every three weeks. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. RESULTS: There were 12 patients who received nab-paclitaxel as the first-line treatment (seven also received carboplatin), and 64 received nab-paclitaxel as the latter-line treatment. The overall ORR, DCR, median PFS, and median OS were 14.5%, 69.7%, 5.2 months, and 12.2 months, respectively. The Eastern Cooperative Oncology Group performance status of one and the age of 70-74 years were independently associated with longer OS, while early treatment line of nab-paclitaxel and age of 70-74 years were independently associated with longer PFS. The most common AEs were anemia, leukopenia, gastrointestinal reaction, fatigue, and peripheral neuropathy, which were all manageable. Dose adjustment or treatment discontinuation was encountered in 10 patients because of AEs. The incidence of AEs was not different among age subgroups. CONCLUSIONS: Nab-paclitaxel has a good clinical response profile in Chinese elderly patients with stage IIIB-IV NSCLC. Prospective clinical trials are needed to confirm these results. KEY POINTS: Significant findings of the study Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has a good clinical response profile in Chinese elderly (≥65 years) patients with stage IIIB-IV non-small-cell lung cancer (NSCLC), with acceptable and manageable adverse events. What this study adds Preliminary evidence shows a good clinical response from treatment with nab-paclitaxel in Chinese elderly patients with advanced NSCLC.

Nomogram to predict cause-specific mortality in extensive-stage small cell lung cancer: A competing risk analysis.

BACKGROUND: Small-cell lung cancer (SCLC) is one of the most aggressive types of lung cancer. The prognosis for SCLC patients depends on many factors. The intent of this study was to construct a nomogram model to predict mortality for extensive-stage SCLC. METHODS: Original data was collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict death probability for extensive-stage SCLC. RESULTS: A total of 16 554 extensive-stage SCLC patients from 2004 to 2014 in the SEER database were included in this study. Gender, race, age, TNM staging (including tumor extent, nodal status, and metastasis), and treatment (surgery, chemotherapy, and radiotherapy) were identified as independent predictors for lung cancer-specific death for extensive-stage SCLC patients. A nomogram model was constructed based on multivariate models for lung cancer related death and other cause related death. Performance of the two models was validated by calibration and discrimination, with C-index values of 0.714 and 0.638, respectively. CONCLUSION: A prognostic nomogram model was established to predict death probability for extensive-stage SCLC. This validated prognostic model may be beneficial for treatment strategy choice and survival prediction.

Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients. METHODS: We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort. RESULTS: In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan-Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively. CONCLUSION: This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach.

Survival comparison of right and left side non-small cell lung cancer in stage I-IIIA patients: A Surveillance Epidemiology and End Results (SEER) analysis.

BACKGROUND: Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non-small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long-term survival in NSCLC patients. METHODS: Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. RESULTS: There was no significant distinction in overall survival (OS) between right (n = 53 496) and left (n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756-1.011; P = 0.432). Left side was associated with superior five-year cancer-specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574-0.9969; P = 0.024). No significant difference was observed in OS (P = 0.689) or CSS (P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side (n = 21 245) was associated with poor OS compared to right side (n = 30 074) NSCLC (HR 1.039, 95% CI 1.011-1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997-1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS (P = 0.986) or CSS (P = 0.979) after PSM analysis. CONCLUSION: The prognosis between right and left side NSCLC in stage I-IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment.