INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.
Humans ; Breast Neoplasms/mortality* ; Retrospective Studies ; Female ; Propensity Score ; Middle Aged ; Adult ; Prognosis ; Disease-Free Survival ; Kaplan-Meier Estimate ; Aged ; Proportional Hazards Models ; Complex Mixtures/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Trametes

BACKGROUND: China is one of the countries with the highest burdens of stomach cancer. The objective of this study was to analyze long-term trends in the incidence and mortality of stomach cancer in Chinese mainland from 1990 to 2019 and to make projections until 2030. METHODS: Data on stomach cancer were extracted from the Global Burden of Diseases Study 2019. Population data were extracted from the Global Burden of Diseases Study 2019 and World Population Prospects 2019. An age-period-cohort framework and decomposition analysis were used in this study. RESULTS: The net drift for the incidence of stomach cancer was 0.2% (95% confidence interval [CI]: 0, 0.4%) per year for men and -1.8% (95% CI: -2.0%, -1.6%) for women. The net drift for mortality was -1.6% (95% CI: -1.8%, -1.3%) per year for men and -3.3% (95% CI: -3.5%, -3.1%) for women. In the last 10-15 years, the risk of stomach cancer occurrence and death has continued to decline for both sexes. Regarding birth cohorts, although the risk of stomach cancer death decreased in general among women and men born after 1920, the risk of occurrence increased in recent birth cohorts (men born after 1970 and women born after 1985). It is expected that the age-standardized incidence will increase among men and decrease among women, and age-standardized mortality will decrease for both sexes. The largest contributor to the projected increase in incident cases and deaths is population aging, and elderly individuals are projected to have an increased proportion of occurrence and death. CONCLUSIONS In the past three decades, the incidence of stomach cancer among men has increased in Chinese mainland, and this trend is projected to continue. Aging will be the main contributor to future increased stomach cancer occurrence and deaths. To reduce the health impact of stomach cancer, more efforts are needed.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Incidence ; Stomach Neoplasms/mortality*

BACKGROUND: Skin cancer is a common skin disease whose incidence and mortality rates have been showing yearly increases. In this report, we update the most recent data on skin cancer as obtained from GLOBOCAN 2022. METHODS: The incidence and mortality rates of skin cancer (melanoma of skin and non-melanoma skin cancer) in GLOBOCAN 2022 were reviewed. These data were analyzed and the characteristics of incidence and mortality across five continents and top five countries and regions in each continent are presented. In addition, correlations between Human Development Index (HDI) and age-standardized incidence and mortality rates of these two skin cancers are described. RESULTS: The GLOBOCAN 2022 data indicated that melanoma was the 17th most common cancer. An estimated 331,722 people were diagnosed with melanoma globally and approximately 58,667 died from this disease. For non-melanoma skin cancer, it ranks as the 5th most common cancer, and an estimated 1,234,533 people were diagnosed with non-melanoma skin cancer globally and approximately 69,416 died from this disease. The incidence of skin cancer varies across geographic regions and countries, with a predominance observed in Oceania, North America, and Europe. Australia was ranked first in terms of incidence, while incidence rates in Africa and Asia were very low. Despite these regional differences in incidence, there was little geographic variation in mortality rates. Currently, the number of deaths from non-melanoma skin cancer exceeds that of melanoma of skin. HDI was positively associated with the incidence of both types of skin cancers, with a positive correlation obtained between HDI and mortality from melanoma of skin and a negative correlation between HDI and mortality from non-melanoma skin cancer. CONCLUSIONS Skin cancer remains a major disease burden worldwide. Substantial variations are observed across countries and regions. Further research on skin cancer will be required to provide a rationale for more effective preventions and treatments of this condition.
Humans ; Skin Neoplasms/mortality* ; Incidence ; Melanoma/mortality* ; Prevalence ; Global Health ; Male ; Female

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*

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

OBJECTIVES: To analyze the disease burden of melanoma among middle-aged and elderly populations in China, and to predict the future trend. METHODS: Data from the Global Burden of Disease (GBD) 2021 were utilized to collect incidence and mortality rates of melanoma, disability-adjusted life years (DALYs), and corresponding age crude rates among the middle-aged and elderly population in China during 1990 and 2021. Additionally, the estimated annual percentage change (EAPC) was employed to assess the temporal trends. Age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models were utilized to compute age, period, and cohort effects on incidence and mortality rates of melanoma, as well as to predict future trends up to 2035. RESULTS: During 1990-2021, the incidence rate of melanoma for males was higher than that for females among the middle-aged and elderly population in China, and the overall incidence rate increased annually with an EAPC of 2.13 (1.90-2.36), while the overall mortality rate and DALY rate showed a declining trend with an EAPC of －0.28 (－0.41-－0.15) and －0.54 (－0.68-－0.41), respectively. The results of the APC model analysis revealed that age effects on both incidence and mortality rates of melanoma in China's middle-aged and elderly population were significant, with both increasing with age. Period and cohort effects showed an upward trend for incidence rates but a downward trend for mortality rates. Moreover, the period and cohort effects for mortality rates were not significant among females. In the BAPC prediction model, the number of incidences of melanoma in middle-aged and elderly people in China would increase dramatically. By 2035, the number of incidence cases is expected to reach approximately 9600 (males) and 10 300 (females), corresponding to an incidence rate of 2.66/10⁵ and 2.67/10⁵, respectively. The number of deaths is projected to be about 2600 (males) and 3500 (females) by 2035, corresponding to a mortality rate of 0.72/10⁵ and 0.91/10⁵, respectively. CONCLUSIONS The disease burden of melanoma among the middle-aged and elderly population in China remains substantial and is expected to increase over the next decade.
Humans ; Melanoma/mortality* ; China/epidemiology* ; Aged ; Middle Aged ; Male ; Female ; Incidence ; Disability-Adjusted Life Years ; Bayes Theorem ; Cost of Illness ; Skin Neoplasms/epidemiology*

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