Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with driver-gene negative advanced non-small cell lung cancer.

BACKGROUND: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP) of first-line immunotherapy as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles best response and progressive mode of first-line immunotherapy could affect the results. PATIENTS AND METHODS: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles best response and progressive mode of first-line immunotherapy were also evaluated. RESULTS: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups in whole population. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p=0.047) 16.1m (16.1 vs 10.8 p=0.039), 16.3m (16.3 vs 10.9 p=0.029) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and oligo progression of first-line immunotherapy. CONCLUSIONS: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and oligo progression in first-line was benefit.

GTSE1: A potential prognostic and diagnostic biomarker in various tumors including lung adenocarcinoma.

OBJECTIVE: This research was aimed to comprehensively investigate the expression levels, diagnostic and prognostic implications, and the relationship with immune infiltration of G2 and S phase-expressed-1 (GTSE1) across 33 tumor types, including lung adenocarcinoma (LUAD), through gene expression profiling. METHODS: GTSE1 mRNA expression data together with clinical information were acquired from Xena database of The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) database for this study. The Wilcoxon rank-sum test was used to detect differences in GTSE1 expression between groups. The ability of GTSE1 to accurately predict cancer status was evaluated by calculating the area under the curve (AUC) value for the receiver operating characteristic curve. Additionally, we investigated the predictive value of GTSE1 in individuals diagnosed with neoplasms using univariate Cox regression analysis as well as Kaplan-Meier curves. Furthermore, the correlation between GTSE1 expression and levels of immune infiltration was assessed by utilizing the Tumor Immune Estimate Resource (TIMER) database to calculate the Spearman rank correlation coefficient. Finally, the pan-cancer analysis findings were validated by examining the association between GTSE1 expression and prognosis among patients with LUAD. RESULTS: GTSE1 exhibited significantly increased expression levels in a wide range of tumor tissues in contrast with normal tissues (p < 0.05). The expression of GTSE1 in various tumors was associated with clinical features, overall survival, and disease-specific survival (p < 0.05). In immune infiltration analyses, a strong correlation of the level of immune infiltration with the expression of GTSE1 was observed. Furthermore, GTSE1 demonstrated good discriminative and diagnostic value for most tumors. Additional experiments confirmed the relationship between elevated GTSE1 expression and unfavorable prognosis in individuals diagnosed with LUAD. These findings indicated the crucial role of GTSE1 expression level in influencing the development and immune infiltration of different types of tumors. CONCLUSIONS: GTSE1 might be a potential biomarker for the prognosis of pan-cancer. Meanwhile, it represented a promising target for immunotherapy.

Efficacy and safety of PD-1/PD-L1 inhibitors in elderly patients with advanced non-small cell lung cancer.

OBJECTIVE: This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC ≥70 years old who received PD-1/PD-L1 inhibitors in our hospital were retrospectively analyzed. According to age, the patient were stratified as follows: 70-75 years old, 76-80 years old, and >80 years old. Kaplan-Meier method was used for survival analysis, and univariate and multivariate Cox proportional hazards regression models were used to analyze the correlation between different clinical characteristics and survival. RESULTS: A total of 58 elderly patients with advanced non-small cell cancer were enrolled in this study. Patients aged 70-75, 76-80, and >80 years old were 32, 19, and 7, respectively. For the all, median OS was 17.0 months, and PFS was 7.0 months. PFS and OS did not differ according to age (P = 0.396, 0.054, respectively). Univariate analysis showed that PS of 0-1, stage III, first-line therapy and irAEs were associated with longer PFS, and PS of 0-1, stage III, and first-line therapy were associated with longer OS. Multivariate analysis showed that patients with stage III had longer PFS. PFS and OS of patients with PS ≥ 2 were significantly shorter than those of patients with PS of 0-1. CONCLUSIONS: In the present real-world retrospective cohort, PD-1/PD-L1 inhibitors are effective and well tolerated in elderly patients with advanced NSCLC. Immunotherapy should be actively used as early as possible in older patients advanced NSCLC.

Does improved nurse staffing impact patient outcomes in cancer? Association between chronic diseases and mortality among older adult patients with lung cancer in Korea.

BACKGROUND: Evidence regarding the impact of nurse staffing on the health outcomes of older adult patients with cancer is scarce. Therefore, this study aimed to evaluate the impact of nurse staffing on long-term and short-term mortality in elderly lung cancer patients. METHODS: This study analyzed data from 5,832 patients with lung cancer in Korea from 2008 to 2018. Nursing grade was considered to assess the effect of nursing staff on mortality in older adult patients with lung cancer. The Cox proportional hazards model was used to evaluate the effect of the initial treatment hospital's nursing grade on one- and five-year mortality. Additionally, economic status and treatment type of patients were analyzed. RESULTS: Approximately 31% of older adult patients with lung cancer died within one year post-diagnosis. Patients in hospitals with superior nursing grades (lower nurse-to-bed ratios) exhibited lower mortality rates. Hospitals with nursing grades 2 and 3 exhibited approximately 1.242-1.289 times higher mortality than grade 1 hospitals. Further, the lower the nursing grade (higher nurse-to-bed ratio), the higher the five-year mortality rate. CONCLUSION: Both short- and long-term mortality rates for older adult patients with lung cancer increased at inferior nursing grades. Treatment in hospitals having inferior nursing grades, upon initial hospitalization, may yield better outcomes. This study provides valuable insight into the quality of adequate staffing to improve the quality of care for elderly cancer patients.

Multidisciplinary meeting review in nonsmall cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure. METHODS: A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase and ClinicalTrials.gov were searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool. RESULTS: 2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30-3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43-4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29-3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21-0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85-3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55-0.72; p<0.00001). DISCUSSION: MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.

Progress against lung cancer, Denmark, 2008-2022.

BACKGROUND AND PURPOSE: There has been marked progress against lung cancer in Denmark. To gain further insight into the different aspects of the improvement, we examined the stage-specific incidence rates, stage-specific survival and mortality rates. MATERIALS AND METHODS: We used information from the Danish Lung Cancer Registry on date of diagnosis and clinical stage to calculate age-standardised incidence rates and patient survival by sex, period and stage. Information about age-standardised lung cancer-specific mortality rates by sex and period was extracted from The Danish Health Data Authority. RESULTS: Firstly, the decrease in incidence rates was due to a reduction in the rates of advanced stages. Secondly, there was a gradual increase in survival across all stages, and thirdly, the mortality rates gradually decreased over time. INTERPRETATION: The improvements in survival and mortality from lung cancer were due to decreasing incidence rates of advanced cancer and improvement in survival at all stages of the disease.

Aspartate Transaminase-to-Albumin Ratio (ATAR), a Novel Prognostic Index, Predicts Outcomes in Patients with Small-Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by high invasion rates, rapid progression, and poor prognoses. Thus, identifying SCLC patients at high risk of progression and death is critical to improve long-term survival. In this study, the aspartate transaminase-to-albumin ratio (ATAR) was examined as a prognostic factor for SCLC patients. METHODS: We screened 196 SCLC patients from December 2013 to September 2022 at the Sichuan Cancer Hospital. The data was collected from patients' medical information as well as from their blood results during diagnosis. Using the Youden index as a cutoff value, patients were divided into high-risk（> 0.54) and low-risk (≤ 0.54) ATAR groups. We analyzed the prognostic factors for overall survival (OS) using the Kaplan-Meier method, univariate and multivariate analyses, Cox regression, and the C-index. RESULTS: There were 109 (55.6%) smokers among the patients, and the median OS was 17.55 months. The Kaplan-Meier analysis indicated that patients with high-risk ATAR had significantly lower OS (p < 0.0001). A multivariate analysis demonstrated that elevated ATAR is an independent adverse predictor of OS (p < 0.001, HR = 1.907). Our study found that ATAR is an independent predictor of survival outcomes in SCLC, which was superior to ALB, PNI, and SII in predicting outcomes in low-risk and high-risk groups (all p < 0.05). Models combining ATAR with ALB, PNI, and SII showed more powerful prognostic value than their corresponding original models. Moreover, the prognostic indicator ATAR can significantly stratify stage I - II and III - IV SCLC patients (p ＜ 0.05). CONCLUSIONS: Peripheral blood ATAR prognostic index can be used as an independent predictor of SCLC patients before treatment.

Prognostic implications of STK11 with different mutation status and its relationship with tumor-infiltrating immune cells in non-small cell lung cancer.

Background: Mutations in STK11 (STK11Mut) gene may present a negative impact on survival in Non-small Cell Lung Cancer (NSCLC) patients, however, its relationship with immune related genes remains unclear. This study is to unveil whether overexpressed- and mutated-STK11 impact survival in NSCLC and to explore whether immune related genes (IRGs) are involved in STK11 mutations. Methods: 188 NSCLC patients with intact formalin-fixed paraffin-embedded (FFPE) tissue available for detecting STK11 protein expression were included in the analysis. After immunohistochemical detection of STK11 protein, patients were divided into high STK11 expression group (STK11High) and low STK11 expression group (STK11Low), and then Kaplan-Meier survival analysis and COX proportional hazards model were used to compare the overall survival (OS) and progression-free survival (PFS) of the two groups of patients. In addition, the mutation data from the TCGA database was used to categorize the NSCLC population, namely STK11 Mutated (STK11Mut) and wild-type (STK11Wt) subgroups. The difference in OS between STK11Mut and STK11Wt was compared. Finally, bioinformatics analysis was used to compare the differences in IRGs expression between STK11Mut and STK11Wt populations. Results: The median follow-up time was 51.0 months (range 3.0 - 120.0 months) for real-life cohort. At the end of follow-up, 64.36% (121/188) of patients experienced recurrence or metastasis. 64.89% (122/188) of patients ended up in cancer-related death. High expression of STK11 was a significant protective factor for NSCLC patients, both in terms of PFS [HR=0.42, 95% CI= (0.29-0.61), P<0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), P<0.001], which was consistent with the finding in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), P<0.001 HR=0.76, 95%CI= (0.65, 0.88), P<0.001]. In TCGA cohort, STK11 mutation was a significant risk factor for NSCLC in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) histology in terms of OS [HR=6.81, 95%CI= (2.16, 21.53), P<0.001; HR=1.50, 95%CI= (1.00, 2.26), P=0.051, respectively]. Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology. Conclusions: Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Evaluating Oral Probiotic Supplements as Complementary Treatment in Advanced Lung Cancer Patients Receiving ICIs: A Prospective Real-World Study.

OBJECTIVE: To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. METHODS: This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). RESULTS: A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. CONCLUSION: Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.

This study examined whether the addition of oral probiotic supplements to ICIs could enhance the treatment of advanced lung cancer. A total of 253 patients with advanced lung cancer were involved in the study, with some receiving probiotics in combination with ICIs and others not. The findings revealed that patients with SCLC who took probiotics had significantly better PFS compared to those who did not. Additionally, there was a tendency towards enhanced PFS in NSCLC patients who received probiotics. In conclusion, the study indicates that incorporating oral probiotics with ICIs may lead to better outcomes for patients with advanced SCLC, although further research is necessary to validate these results.This real world study explores whether oral probiotic supplements along with immune checkpoint inhibitors (ICIs) can help treat advanced lung cancer. The study included 253 patients with advanced lung cancer receiving ICIs treatment, part of them taking probiotics along with ICIs. The results showed that patients with small cell lung cancer (SCLC) who took probiotics had better progression-free survival (PFS) compared to those who didn't. There was also a trend towards better PFS in non-small cell lung cancer (NSCLC) patients who took probiotics. Overall, the study suggests that taking oral probiotics along with ICIs may improve outcomes for patients with advanced SCLC, but more research is needed to confirm these findings.

[Impact of changes in malignant tumor death spectrum on life expectancy in Tianjin residents from 1999-2019].

Objective: To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or rural) in Tianjin from 1999 to 2019. Methods: The Abridged Life Table method and the Arriaga's decomposition method were used to calculate the effects of changes in spectrum of deaths from malignant tumors on the life expectancies of Tianjin residents of different ages, sexes, and regions. Results: During 1999-2019, the life expectancies increased by 4.96 years and 5.69 years for males and females, respectively, in Tianjin. The decreases in the mortalities from malignant neoplasms contributed 0.12 year (3.30%) and 0.03 year (0.77%) for males and females, respectively, to the increase during 1999-2007, and 0.05 year (3.13%) and 0.12 year (6.08%) for males and females, respectively, during 2007-2019. The decreases in the mortality rates of malignant tumors contributed the most to the increase among residents in the 60-69 years group, and the decreases in mortality rates of lung, gastric, esophageal, and liver cancers had relatively larger contribution. Lung cancer had a negative effect on the life expectancies of men and rural residents, but a positive effect on those of women and urban residents. The significant increases in the mortality rates of lung, colorectal, and pancreatic cancers in the ≥85 years group had a large negative effect on the overall life expectancy. Breast and ovarian cancers contributed negatively to the life expectancy of female residents. Conclusion: The overall increase in the life expectancy in Tianjin from 1999 to 2019 was mainly attributed to the elderly and the decreases in the mortality rates of gastric, esophageal, and liver cancers, among other malignancies, while the increases in the mortality rates of lung, colorectal, gallbladder, pancreatic, and breast cancers were the most significant factors hindering the increase of the life expectancy in Tianjin.

Efficacy and safety of different immunotherapies combined with chemotherapy as first-line therapy in patients with small cell lung cancer: a network meta-analysis.

Background: The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies. Objective: This study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer. Method: We searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate. Results: This meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%). Conclusions: According to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.

Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.

Background: Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. Currently, the relationship between ALI and the prognosis of stroke patients was not yet known. The purpose of the current study was to estimate their relationship. Methods: Cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were collected. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis. Results: 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI. Conclusion: This was the first study on the relationship between ALI and all-cause and CVD mortality in stroke patients. Elevated ALI was closely associated with a reduced risk of all-cause mortality. A reverse J-shaped non-linear relationship existed between the two, with an inflection point at 83.76. These findings implied that controlling the ALI of stroke patients within an appropriate range was crucial for their prognosis (such as weight management, albumin supplementation, anti-inflammatory treatment). The dynamic variation in ALI was also advantageous for clinicians in establishing personalized ALI criteria to maximize the long-term survival of stroke patients.

Integration of multi-omics data for survival prediction of lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: The morbidity of lung adenocarcinoma (LUAD) has been increasing year by year and the prognosis is poor. This has prompted researchers to study the survival of LUAD patients to ensure that patients can be cured in time or survive after appropriate treatment. There is still no fully valid model that can be applied to clinical practice. METHODS: We introduced struc2vec-based multi-omics data integration (SBMOI), which could integrate gene expression, somatic mutations and clinical data to construct mutation gene vectors representing LUAD patient features. Based on the patient features, the random survival forest (RSF) model was used to predict the long- and short-term survival of LUAD patients. To further demonstrate the superiority of SBMOI, we simultaneously replaced scale-free gene co-expression network (FCN) with a protein-protein interaction (PPI) network and a significant co-expression network (SCN) to compare accuracy in predicting LUAD patient survival under the same conditions. RESULTS: Our results suggested that compared with SCN and PPI network, the FCN based SBMOI combined with RSF model had better performance in long- and short-term survival prediction tasks for LUAD patients. The AUC of 1-year, 5-year, and 10-year survival in the validation dataset were 0.791, 0.825, and 0.917, respectively. CONCLUSIONS: This study provided a powerful network-based method to multi-omics data integration. SBMOI combined with RSF successfully predicted long- and short-term survival of LUAD patients, especially with high accuracy on long-term survival. Besides, SBMOI algorithm has the potential to combine with other machine learning models to complete clustering or stratificational tasks, and being applied to other diseases.

Clinical relevance of somatic mutations in Chinese lung adenocarcinoma and their prognostic implications for survival.

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.

Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

BACKGROUND: Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. METHODS: We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). RESULTS: Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. CONCLUSION: DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

High incidence of lung cancer death after curative endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. METHODS: This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. RESULTS: The 5-year survival rate of 187 patients was 92.6% during a median follow-up duration of 96.8 months. Thirty-one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p < 0.001). Patients with second primary lung cancer (LC) had a high mortality rate (56.3%). Univariate and multivariate analyses showed that multiple Lugol-voiding lesions (LVLs) tended to be associated with SPMs (p = 0.077, hazard ratio [HR] 4.43, 95% confidence interval [CI]: 0.91-6.50), and metachronous ESCC was an independent risk factor for the incidence of second primary LC (p = 0.037, HR 3.51, 95% CI: 1.08-11.41). CONCLUSIONS: SPMs that cannot be detected by EGD, such as LC, must be considered after the curative resection of ESCC. We suggest strict screening by both EGD and computed tomography for patients with multiple LVLs or metachronous ESCC to detect SPMs in their early stages.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study.

PURPOSE: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. MATERIALS AND METHODS: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding. RESULTS: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025). CONCLUSION: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study.

BACKGROUND: It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks. METHODS: This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1 <0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks. RESULTS: The study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1 values. CONCLUSION: Impaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.