BACKGROUND: Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients' clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens. METHODS: This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients. RESULTS: With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS ( P = 0.012) and EFS ( P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs . 6 [4, 7] days, Z = -0.227, P = 0.820). CONCLUSIONS NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Female ; Lung Neoplasms/mortality* ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy/methods* ; Retrospective Studies ; Aged ; Adult ; Kaplan-Meier Estimate ; Treatment Outcome ; Immunotherapy/methods*

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

BACKGROUND: Neoadjuvant immunochemotherapy has emerged as an indispensable therapeutic modality for non-small cell lung cancer (NSCLC). However, its clinical application experience remains limited, and the associations between various clinical factors and treatment benefits remain undefined. This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with stage IB-IIIB NSCLC in a real-world setting, analyze survival outcomes among subgroups with diverse clinical characteristics, and identify potential clinical predictive factors for pathological response. METHODS: This study included patients with stage IB-IIIB NSCLC who underwent radical lung resection after 2-4 cycles of neoadjuvant immunochemotherapy at Peking University People's Hospital between August 2019 and March 2024. Medical records and follow-up information were collected to analyze therapeutic response, adverse events and survival outcomes. Logistic analysis was used to identify clinical predictors of pathological response. RESULTS: Among 183 enrolled patients, 116 (63.4%) were stage III. Grade 3-4 immune-related adverse events (irAEs) occurred in 39 (21.3%) patients. Radiographic complete response (CR) or partial response (PR) was achieved in 118 (64.5%) patients. R0 resection was achieved in 180 (98.4%) patients. Major pathologic response (MPR) was observed in 107 (58.5%) patients, with 78 (42.6%) achieving pathologic complete response (pCR). Squamous cell carcinoma and radiographic objective response were associated with pathological response (pCR/MPR). With a median follow-up of 22.1 [interquartile range (IQR): 18.3-32.2] months, the 2-year event-free survival (EFS) and overall survival (OS) rates were 82.5% and 90.4%, respectively. Achievement of pathological response (pCR/MPR) was correlated with prolonged survival outcomes. CONCLUSIONS Neoadjuvant immunochemotherapy is safe and effective for patients with stage IB-IIIB NSCLC. Patients achieving pCR or MPR exhibit significantly better survival benefits from neoadjuvant immunochemotherapy. Squamous cell carcinoma and radiographic objective response can serve as clinical predictors of pathological response.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Lung Neoplasms/mortality* ; Female ; Middle Aged ; Neoadjuvant Therapy/adverse effects* ; Aged ; Neoplasm Staging ; Adult ; Immunotherapy/adverse effects* ; Treatment Outcome ; Retrospective Studies

BACKGROUND: Lung cancer ranks as the foremost cause of cancer-related deaths in China, significantly undermining population health and longevity. By analyzing the trends of death and years of life lost caused by lung cancer in Handan from 2017 to 2023, data support is provided for the formulation of prevention and treatment strategies. METHODS: Lung cancer death data in Handan during 2017-2023 were collected. Excel 2010, SPSS 26.0 and Joinpoint 4.9.0.0 were used to analyze the mortality rate of lung cancer, average annual percentage change (AAPC), cause eliminated life expectancy (CELE), potential gains in life expectancy (PGLEs), Fulfillment index, potential years of life lost (PYLL), potential years of life lost rate (PYLLR), and standardized potential years of life lost rate (SPYLLR). RESULTS: The standardized mortality rate of lung cancer in Handan from 2017 to 2023 showed a decreasing trend (AAPC=-7.10%, P<0.01). The CELE of lung cancer increased by 2.49 years (AAPC=0.48%, P<0.05). The life loss rate decreased by 21.43% (AAPC=-4.61%, P<0.05). The Fulfillment index by lung cancer increased with the growth of age from 2017 to 2023. The PYLL, PYLLR, standardized potential years of life lost (SPYLL) and SPYLLR of lung cancer during 2017 to 2023 were 134,219.75 person years, 2.03‰, 98,735.63 person years, and 1.49‰, respectively. The annual PYLLR and SPYLLR showed a decreasing trend (AAPC=-6.34%, -9.34%, respectively, P<0.01). CONCLUSIONS The standardized mortality rate of lung cancer in Handan from 2017 to 2023 showed a decreasing trend, and the impact of lung cancer on life expectancy decreased. The mortality rates of lung cancer showed significant differences among different ages and genders. It is necessary to take good measures to prevent and control lung cancer in males and higher age groups.
Lung Neoplasms/mortality* ; Humans ; Male ; Life Expectancy/trends* ; Female ; China/epidemiology* ; Aged ; Middle Aged ; Aged, 80 and over ; Adult ; Young Adult

BACKGROUND: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an exceedingly rare malignancy originating from bronchial submucosal glands, accounting for <0.2% of lung cancers. Histologically characterized by a triphasic composition of mucinous, epidermoid, and intermediate cells, PMEC is classified into low-grade (favorable prognosis) and high-grade (aggressive behavior) subtypes. This study aimed to investigate the clinicopathological characteristics and prognostic indicators of PMEC. METHODS: Clinicopathological, radiological, molecular, and survival data from 26 PMEC patients were retrospectively analyzed, including immunohistochemical profiles and MAML2 rearrangement status, supplemented by literature review. RESULTS: The cohort comprised 14 males and 12 females (mean age: 55.6 years). Eight patients (30.8%) were smokers, and 19 (73.1%) presented with symptoms. Central tumors predominated (n=19, 73.1%) versus peripheral lesions (n=7, 26.9%). Computed tomography (CT) imaging consistently revealed hypo-to-isodense masses/nodules. Pathologically, 19 cases were low-grade and 7 high-grade. Immunohistochemically, the tumor cells were positive for CK7, P40, P63 and CK5/6, and the Ki-67 index ranged from 2% to 70%. MAML2 rearrangement was detected in 52.4% (11/21) of tested cases. Clinical staging distribution: stage I (n=14), stage II (n=8), stage III (n=3), stage IV (n=1). Treatment modalities: radical surgery alone (n=13), surgery with adjuvant chemotherapy (n=11), chemoradiotherapy (n=1), and conservative management (n=1). With a median follow-up of 57 months, 6 patients (23.1%) died. Prognostic analysis demonstrated: (1) Significantly inferior survival in high-grade versus low-grade groups (P<0.05); (2) Lymph node metastasis, advanced stage, Ki-67>20%, and high-grade histology significantly correlated with reduced overall survival (P<0.05); (3) Lymph node metastasis constituted an independent poor prognostic factor (HR=12.73, 95%CI: 1.22-132.96). CONCLUSIONS PMEC exhibits distinct clinicopathological features, with MAML2 rearrangement present in approximately half of cases. Lymph node metastasis, advanced stage, high Ki-67 proliferation index, and high-grade histology are key determinants of poor prognosis, with lymph node metastasis serving as an independent risk factor.
Humans ; Male ; Female ; Middle Aged ; Carcinoma, Mucoepidermoid/mortality* ; Lung Neoplasms/mortality* ; Trans-Activators/genetics* ; Prognosis ; Adult ; Gene Rearrangement ; Aged ; Retrospective Studies ; Transcription Factors/genetics* ; DNA-Binding Proteins/genetics*

BACKGROUND: Tracheal, bronchus, and lung cancer (TBL) is a major cause of mortality and top contributor to productivity loss in large emerging economies such as the BRICS (Brazil, Russia, India, China, and South Africa). We examined the time trends of TBL mortality across the BRICS to better understand the disease burden in these countries and inform public health and healthcare resource allocation. METHODS: TBL mortality-related data between 1990 and 2019 were obtained from the Global Burden of Disease Study 2019 and analyzed using age-period-cohort models. Net drift (local drift) was used to describe the expected age-adjusted TBL mortality rate over time overall (each age group); the longitudinal age curve was used to reflect the age effect; the period rate ratios (RRs) were used to reflect the period effect; and the cohort RR was used to reflect the cohort effect. RESULTS: In 2019, there were 958.3 thousand TBL deaths across the BRICS, representing 46.9% of the global TBL deaths. From 1990 to 2019, the age-standardized mortality rate (ASMR) of TBL decreased in Russia, Brazil, and South Africa while increased in China and India, with the largest reduction reported in Russia (-29.6%) and the largest increase in China (+22.4%). India showed an overall increase (+15.7%) in TBL mortality but the mortality risk decreased among individuals born after 1990 (men) and 1995 (women). Although South Africa and Brazil experienced an overall decline in TBL mortality, their recent birth cohorts, such as Brazilian individuals born after 1985 (men) and 1980 (women), and South African men born after 1995, had an increasing TBL mortality risk. China has experienced an overall increase in TBL mortality, with the mortality risk rising among individuals born after 1995 for both men and women. Russia, which had the highest TBL mortality among the BRICS countries in 1990, has demonstrated significant improvement over the past three decades. CONCLUSIONS Over the past 30 years, the BRICS accounted for an increasing proportion of global TBL mortality. TBL mortality increased in older women in all the BRICS countries except Russia. Among the recent birth cohort, the risk of TBL mortality increased in Brazil, China, and South Africa. More effective efforts are needed in the BRICS to reduce the burden of TBL and help achieve the United Nation's Sustainable Development Goals.
Humans ; Lung Neoplasms/mortality* ; Male ; Female ; China/epidemiology* ; Middle Aged ; Global Burden of Disease ; Aged ; India/epidemiology* ; Adult ; South Africa/epidemiology* ; Cohort Studies ; Russia/epidemiology* ; Brazil/epidemiology* ; Tracheal Neoplasms/mortality* ; Bronchial Neoplasms/mortality* ; Adolescent ; Young Adult ; Aged, 80 and over ; Child

BACKGROUND: Cancer patterns in China are becoming similar to those in the United States (US). Comparing the recent cancer profiles, trends, and determinants in China and the US can provide useful reference data. METHODS: This study used open-source data. We used GLOBOCAN 2022 cancer estimates and United Nations population estimates to calculate cancer cases and deaths in both countries during 2024. Data on cancer incidence and mortality trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) program and National Centre for Health Statistics in the US and cancer registry reports of the National Cancer Center (NCC) of China. Data from the Global Burden of Disease study (GBD) and a decomposition approach were used to estimate the contributions of four determinants to the change in cancer deaths. RESULTS: In 2024, there are an estimated 3,246,625 and 2,510,597 new cancer cases and 1,699,066 and 640,038 cancer deaths in China and the US, respectively. The highest estimated cancer cases are lung cancer in China and breast cancer in the US. The age-standardized incidence rates of lung and colorectal cancer in the US, and stomach, liver, and esophageal cancer in China have decreased, but the incidence rates of liver cancer in the US and colorectal cancer, prostate cancer in men, and cervical cancer in women in China have increased. Increases in the adult population size and population aging are main reasons for the increase in cancer deaths; case fatality rates are a main reason for the decrease in cancer deaths in both countries. CONCLUSIONS China has made progress in cancer control but lags the US. Considering the transformation in China's pattern of cancers epidemiology, it is imperative to develop stronger policies by adopting the cancer prevention and control strategies used in the US to address population aging and curb growing cancer trends.
Humans ; China/epidemiology* ; United States/epidemiology* ; Male ; Neoplasms/mortality* ; Female ; Incidence ; SEER Program ; Middle Aged ; Adult ; Aged ; Lung Neoplasms/mortality*

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is a malignant tumor with remarkable proliferative and invasive ability, which has very poor clinical prognosis due to lack of effective treatments. This study aims to evaluate the efficacy and synergistic effects of radiotherapy (RT) combined with immunotherapy (IT) and chemotherapy (CT) in patients with ES-SCLC. METHODS: A retrospective analysis was performed on 145 ES-SCLC patients treated with first-line CT. Kaplan-Meier analysis and Log-rank tests were used to evaluate survival outcomes, while propensity score matching (PSM) was applied to reduce confounding factors. RESULTS: The median overall survival (mOS) and median progression-free survival (mPFS) for the entire cohort were 15.7 and 6.9 mon, respectively. The IT+CT group had a significantly longer mOS compared to the CT group (17.2 vs 13.5 mon, P=0.047). Similarly, the RT+CT group demonstrated superior mOS (18.5 vs 12.3 mon, P<0.001) and mPFS (7.1 vs 6.2 mon, P=0.006) compared to the CT group. Multivariate analysis identified RT, IT, and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for mOS (P<0.05), while gender and ECOG PS were independent predictors for mPFS (P<0.05). Following PSM, the RT+CT group continued to exhibit significant advantages in mOS (18.0 vs 12.1 mon, P<0.001) and mPFS (7.1 vs 5.5 mon, P=0.037) compared to the CT group. Notably, the RT+IT+CT group achieved a markedly longer mOS than the IT+CT group (28.5 vs 15.8 mon, P=0.017). Grade 3-4 adverse events occurred in 27.6% of patients, with no grade 5 adverse events reported. CONCLUSIONS The combination of RT, IT, and CT significantly enhances the prognosis of ES-SCLC patients. RT plays a key role in their synergistic effects and demonstrates good safety, warranting further research and clinical application.
Humans ; Small Cell Lung Carcinoma/mortality* ; Male ; Female ; Middle Aged ; Lung Neoplasms/mortality* ; Retrospective Studies ; Aged ; Immunotherapy ; Prognosis ; Combined Modality Therapy ; Adult ; Neoplasm Staging ; Aged, 80 and over

BACKGROUND: A prognostic nutritional index (PNI) developed by nutritional status and inflammation are closely associated with poor prognosis in malignant tumors. However, the predictive impact of PNI in patients with malignant pleural effusion (MPE) remains inconclusive. The study aimed to determine the predictive value of PNI in prognosis and spontaneous pleurodesis among patients with MPE. METHODS: The patients diagnosed with advanced non-small cell lung cancer (NSCLC) with MPE in West China Hospital between January 2015 and December 2022 were reviewed and allocated randomly to development set(60%) and validation set(40%). After collecting clinical data, peripheral blood inflammation indices and calculating systemic inflammation indices, the effects of PNI on prognosis and spontaneous pleurodesis have been evaluated by Cox proportional hazards models, Kaplan-Meier method and Nelson-Aalen cumulative risk curve. RESULTS: In total, 261 patients diagnosed NSCLC with MPE were selected (development set: n=157; validation set: n=104), of whom 58.2% were aged <65 years, 53.6% were male and 95.8% were diagnosed with adenocarcinoma. The dichotomous cut-off value for PNI was 44.1, respectively. Compared with lower PNI (PNI<44.1) cases, patients with higher PNI (PNI≥44.1) showed significantly longer overall survival (36.5 vs 24.3 mon, P=0.02) and higher incidence of spontaneous pleurodesis (P=0.009). According to the multivariate Cox analysis, higher PNI was associated with good prognosis and successful spontaneous pleurodesis (P<0.05). According to the results of Cox regression analysis, the PNI-prognosis and PNI-spontaneous pleurodesis models are determined, the receiver operating characteristic (ROC) curves are drawn, and the area under the curves (AUC) value of development set are 0.694 (95%CI: 0.620-0.776) and 0.673 (95%CI: 0.590-0.737). CONCLUSIONS PNI is a reliable biomarker of prognosis and spontaneous pleurodesis in patients with MPE. Attention to the patient's nutritional status and inflammation may improve the prognosis and efficacy of pleural effusion.
Humans ; Male ; Female ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/mortality* ; Lung Neoplasms/mortality* ; Aged ; Prognosis ; Pleurodesis ; Pleural Effusion, Malignant/mortality* ; Nutrition Assessment ; Adult ; Nutritional Status

BACKGROUND: Although change in the birth cohort effect on cancer mortality rates is known to be highly associated with the decreasing rates of age-standardized cancer mortality rates in Japan, the differences in the trends of cohort effect for representative cancer types among the prefectures remain unknown. This study aimed to investigate the differences in the decreasing rate of cohort effects among the prefectures for representative cancer types using age-period-cohort (APC) analysis. METHODS: Data on stomach, colorectal, liver, and lung cancer mortality for each prefecture and the population data from 1999 to 2018 were obtained from the Vital Statistics in Japan. Mortality data for individuals aged 50 to 79 years grouped in 5-year increments were used, and corresponding birth cohorts born 1920-1924 through 1964-1978 were used for analysis. We estimated the effects of age, period, and cohort on each type of mortality rate for each prefecture by sex. Then, we calculated the decreasing rates of cohort effects for each prefecture. We also calculated the mortality rate ratio of each prefecture compared with all of Japan for cohorts using the estimates. RESULTS: As a result of APC analysis, we found that the decreasing rates of period effects were small and that there was a little difference in the decreasing rates among prefectures for all types of cancer among both sexes. On the other hand, there was a large difference in the decreasing rates of cohort effects for stomach and liver cancer mortality rates among prefectures, particularly for men. For men, the decreasing rates of cohort effects in cohorts born between 1920-1924 and 1964-1978 varied among prefectures, ranging from 4.1 to 84.0% for stomach cancer and from 20.2 to 92.4% for liver cancers, respectively. On the other hand, the differences in the decreasing rates of cohort effects among prefectures for colorectal and lung cancer were relatively smaller. CONCLUSIONS The decreasing rates of cohort effects for stomach and liver cancer varied widely among prefectures. It is possible that this will influence cancer mortality rates in each prefecture in the future.
Aged ; Cohort Studies ; Colorectal Neoplasms/mortality* ; Female ; Humans ; Japan/epidemiology* ; Liver Neoplasms/mortality* ; Lung Neoplasms/mortality* ; Male ; Middle Aged ; Risk Factors ; Stomach Neoplasms/mortality*