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.

Effects of joint screening for prostate, lung, colorectal, and ovarian cancer - results from a controlled trial.

Background: Although screening is widely used to reduce cancer burden, untargeted cancers are frequently missed after single cancer screening. Joint cancer screening is presumed as a more effective strategy to reduce overall cancer burden. Methods: Gender-specific screening effects on PLCO cancer incidence, PLCO cancer mortality, all-neoplasms mortality and all-cause mortality were evaluated, and meta-analyses based on gender-specific screening effects were conducted to achieve the pooled effects. The cut-off value of time-dependent receiver-operating-characteristic curve of 10-year combined PLCO cancer risk was used to reclassify participants into low- and high-risk subgroups. Further analyses were conducted to investigate screening effects stratified by risk groups and screening compliance. Results: After a median follow-up of 10.48 years for incidence and 16.85 years for mortality, a total of 5,506 PLCO cancer cases, 1,845 PLCO cancer deaths, 3,970 all-neoplasms deaths, and 14,221 all-cause deaths were documented in the screening arm, while 6,261, 2,417, 5,091, and 18,516 outcome-specific events in the control arm. Joint cancer screening did not significantly reduce PLCO cancer incidence, but significantly reduced male-specific PLCO cancer mortality (hazard ratio and 95% confidence intervals [HR(95%CIs)]: 0.88(0.82, 0.95)) and pooled mortality [0.89(0.84, 0.95)]. More importantly, joint cancer screening significantly reduced both gender-specific all-neoplasm mortality [0.91(0.86, 0.96) for males, 0.91(0.85, 0.98) for females, and 0.91(0.87, 0.95) for meta-analyses] and all-cause mortality [0.90(0.88, 0.93) for male, 0.88(0.85, 0.92) for female, and 0.89(0.87, 0.91) for meta-analyses]. Further analyses showed decreased risks of all-neoplasm mortality was observed with good compliance [0.72(0.67, 0.77) for male and 0.72(0.65, 0.80) for female] and increased risks with poor compliance [1.61(1.40, 1.85) for male and 1.30(1.13, 1.40) for female]. Conclusion: Joint cancer screening could be recommended as a potentially strategy to reduce the overall cancer burden. More compliance, more benefits. However, organizing a joint cancer screening not only requires more ingenious design, but also needs more attentions to the potential harms. Trial registration: NCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian).

Biomarkers for predicting the severity of spinal cord injury by proteomic analysis.

Purpose: Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity. Methods: SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay. Results: After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM. Conclusion: Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Associations of chest X-ray trajectories, smoking, and the risk of lung cancer in two population-based cohort studies.

Objectives: Despite the increasing use of computed tomography (CT), chest X-ray (CXR) remains the first-line investigation for suspected lung cancer (LC) in primary care. However, the associations of CXR trajectories, smoking and LC risk remain unknown. Methods: A total of 52,486 participants from the PLCO and 22,194 participants from the NLST were included. The associations of CXR trajectories with LC risk were evaluated with multivariable COX regression models and pooled with meta-analyses. Further analyses were conducted to explore the stratified associations by smoking status and the factors associated with progression and regression in CXR. Results: Compared to stable negative CXR (CXRSN), HRs (95%CIs) of LC incidence were 2.88(1.50-5.52), 3.86(2.03-7.35), and 1.08(0.80-1.46) for gain of positive CXR (CXRGP), stable positive CXR (CXRSP), and loss of positive CXR (CXRLP), while the risk of LC mortality were 1.58(1.33-1.87), 2.56(1.53-4.29), and 1.05(0.89-1.25). Similar trends were observed across different smoking status. However, LC risk with CXRGP overweighed that with CXRSP among ever smokers [2.95(2.25-3.88) vs. 2.59(1.33-5.02)] and current smokers [2.33(1.70-3.18) vs. 2.26(1.06-4.83)]. Moreover, compared to CXRSN among never smokers, even no progression in CXR, the HRs(95%CIs) of LC incidence were 7.39(5.60-9.75) and 31.45(23.58-41.95) for ever and current smokers, while risks of LC mortality were 6.30(5.07-7.81) and 27.17(21.65-34.11). If participants gained positive CXR, LC incidence risk significantly climbed to 22.04(15.37-31.60) and 71.97(48.82-106.09) for ever and current smokers, while LC mortality risk climbed to 11.90(8.58-16.50) and 38.92(27.04-56.02). CXRLP was associated with decreased LC risk. However, even smokers lost their positive CXR, and the increased risks of LC incidence and mortality did not decrease to non-significant level. Additionally, smoking was significantly associated with increased risk of CXRGP but not CXRLP. Conclusion: LC risk differed across CXR trajectories and would be modified by smoking status. Comprehensive intervention incorporating CXR trajectories and smoking status should be recommended to reduce LC risk.

Risk-stratified multi-round PSA screening for prostate cancer integrating the screening reference level and subgroup-specific progression indicators.

BACKGROUND: Although prostate-specific antigen (PSA) is widely used in prostate cancer (PCa) screening, nearly half of PCa cases are missed and less than one-third of cases are non-lethal. Adopting diagnostic criteria in population-based screening and ignoring PSA progression are presumed leading causes. METHODS: A total of 31,942 participants with multi-round PSA tests from the PLCO trial were included. Time-dependent receiver-operating-characteristic curves and area under curves (tdAUCs) were performed to determine the screening reference level and the optimal subgroup-specific progression indicator. Effects of risk-stratified multi-round PSA screening were evaluated with multivariable Cox regression and measured with hazard ratio [HR (95%CIs)]. RESULTS: After a median follow-up of 11.6 years, a total of 3484 PCa cases and 216 PCa deaths were documented. The tdAUC of 10-year incidence PCa with PSA was 0.816, and the cut-off value was 1.61 ng/ml. Compared to subgroup with stable negative PSA in both first-round (FR) and last-round (LR) tests [FR(-)/LR(-)], HRs (95%CI) of PCa incidence were 1.66 (1.20-2.29), 8.29 (7.25-9.48), and 14.52 (12.95-16.28) for subgroups with loss of positive PSA[FR(+)/LR(-)], gain of positive PSA[FR(-)/LR(+)], and stable positive PSA[FR(+)/LR(+)]; while HRs(95%CI) of PCa mortality were 1.47 (0.52-4.15), 5.71 (3.68-8.86), and 5.01 (3.41-7.37). After excluding regressive PSA [(namely FR(+)/LR(-)], absolute velocity was the shared optimal progression indicator for subgroups with FR(-)/LR(-), FR(-)/LR(+), and FR(+)/LR(+), with tdAUCs of 0.665, 0.681 and 0.741, and cut-off values of 0.07, 0.21, and 0.33 ng/ml/year. After reclassifying participants into groups with positive and negative progression based on subgroup-specific progression indicators, incidence HR (95%CI) were 2.41 (1.87-3.10), 2.91 (2.43-3.48), and 3.16 (2.88-3.46) for positive progression compared to negative progression within subgroups of FR(-)/LR(-), FR(-)/LR(+), and FR(+)/LR(+), while mortality HR (95%CI) were 2.22 (0.91-5.38), 2.37 (1.28-4.38), and 2.98 (1.94-4.59). To improve screening performances by excluding regressive PSA and low-risk positive progression in FR(-)/LR(-), optimized screening strategy not only significantly reduce 32.4% of missed PCa (54.0% [1881/3484] vs. 21.6% [754/3484], P < 0.001), but also detected additional 8.0% of high-grade PCa (Gleason score 7-10: 36.0% [665/1849] vs. 28.0% [206/736], P < 0.001) than traditional screening strategy. CONCLUSIONS: Risk-stratified multi-round PSA screening strategy integrating the screening reference level and the optimal subgroup-specific progression indicator of PSA could be recommended as a fundamental strategy to reduce missed diagnosis and improve the detection of high-grade PCa cases.

Comparisons of clinical characteristics, prognosis, epidemiological factors, and genetic susceptibility between HER2-low and HER2-zero breast cancer among Chinese females.

BACKGROUND: Traditional human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) is recommended to be divided into HER2-low and HER2-zero subtypes due to different prognosis. However, few studies investigated their differences in clinical characteristics and prognosis among Chinese HER2-negative BC and their stratified differences by hormone receptor (HR), while fewer studies investigated their differences in epidemiological factors and genetic susceptibility. METHODS: A total of 11,911 HER2-negative BC were included to compare the clinical characteristics and prognosis between HER2-zero and HER2-low BC, and 4227 of the 11,911 HER2-negative BC were further compared to 5653 controls to investigate subtype-specific epidemiological factors and single nucleotide polymorphisms(SNPs). RESULTS: Overall, 64.2% of HER2-negative BC were HER2-low BC, and the stratified proportions of HER2-low BC were 61.9% and 75.2% for HR-positive and HR-negative BC, respectively. Compared to HER2-zero BC, HER2-low BC among HR-positive BC showed younger age at diagnosis, later stage, poorer differentiation, and higher Ki-67, while elder age at diagnosis and lower mortality were observed for HER2-low BC among HR-negative BC (all p values <0.05). Compared to healthy controls, both HER2-low and HER2-zero BC are associated with similar epidemiological factors and SNPs. However, stronger interaction between epidemiological factors and polygenic risk scores were observed for HER2-zero BC than HER2-low BC among either HR-positive [odds ratios: 10.71 (7.55-15.17) and 8.84 (6.19-12.62) for the highest risk group compared to the lowest risk group] or HR-negative BC [7.00 (3.14-15.63) and 5.70 (3.26-9.98)]. CONCLUSIONS: HER2-low BC should deserve more attention than HER2-zero BC, especially in HR-negative BC, due to larger proportion, less clinical heterogeneity, better prognosis, and less susceptibility to risk factors.

The changes of subtype markers between first and second primary breast cancers.

BACKGROUND: Previous studies investigated the changes of subtype markers [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)] in several clinical settings, but not for second primary breast cancer (SPBC) after first primary breast cancer (FPBC). METHODS: A total of 15,390 patients with SPBC were preliminarily selected from the Surveillance, Epidemiology, and End Results Program, and 3777 patients with complete information on three subtype markers in both FPBC and SPBC were included in the final analyses. The changes of subtype markers and their prognostic implications and potential influential factors were well investigated. RESULTS: The overall change rates of ER, PR, and HER2 between FPBC and SPBC were 23.0% (867/3777), 35.0% (1322/3777), and 18.3% (691/3777), respectively. Gains of ER, PR, and HER2 after negative index markers were 48.7% (364/748), 37.9% (418/1103), and 11.5% (370/3211), while losses of markers after positive index markers were 16.6% (503/3029), 33.8%(904/2674), and 56.7%(321/566). Loss of ER was significantly associated with increased mortality (18.1% vs. 7.9%, p < 0.001), while gain of ER was significantly associated with decreased mortality (11.5% vs. 23.2%, p < 0.001). Similar results were observed for changes of PR status. However, loss of HER2 was significantly associated with decreased mortality (8.7% vs. 16.3%, p = 0.014), and no significant association was observed between the gain of HER2 and the prognosis of SPBC. Multivariate competing risk analyses showed similar results. HER2 status in FPBC, chemotherapy, and radiotherapy was significantly associated with changes of ER/PR (all p < 0.05), and no available therapies associated with HER2 change. CONCLUSION: The changes of subtype markers are observed in a considerable proportion of patients and has statistically significant prognostic implications. Biopsies should be taken as a routine procedure for better therapy management.

Development of a modified ABC method among Helicobacter pylori infected but serum pepsinogen test-negative individuals.

BACKGROUND: Although the ABC method for gastric cancer (GC) screening has been widely adopted in Japan, it may not be suitable for other countries due to population heterogeneity and different tumor histology. We aim to develop a modified ABC method to improve GC screening performance, especially among Helicobacter pylori (Hp) infected but serum pepsinogen (sPG) test-negative individuals. METHODS: A total of 4745 participants were recruited from Tianjin, China, and were classified into four groups by combined assay for Hp infection and sPG concentrations: Group A (Hp [-], PG [-]), Group B (Hp [+], PG [-]), Group C (Hp [+], PG [+]), and Group D (Hp [-], PG [+]). We used receiver-operating characteristic (ROC) curves analysis and minimum p value method to determine the optimal cutoff point for PG II in Group B. We performed logistic regressions to examine the risk of GC across different subgroups. In addition to the derivation set, the performance of the modified ABC method was also evaluated in an external set involving 16,292 participants from Liaoning, China. RESULTS: In the modified ABC method, we further classified Group B as low-risk (Group B1) and high-risk subgroups (Group B2) using optimal sPG II cutoff point (20.0 ng/mL) by ROC curves analysis and minimum p value method. Compared with Group B1, Group B2 had a significantly higher risk of GC (adjusted OR = 2.54, 95% CI = 1.94-3.33). The modified ABC method showed good discrimination for GC (AUC = 0.61, 95% CI = 0.59-0.63) and improved risk reclassification (NRI = 0.11, p < .01). Similar results were observed in the validation dataset. CONCLUSIONS: The modified ABC method can effectively identify high-risk population for GC among Hp-infected but sPG test-negative participants in China.

Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors.

Background: Previous studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death. Methods: Time trends in the proportions of CV death (PCV), cancer death (PCA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMRCV) began to outweigh the cumulative cancer mortality rate (CMRCA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death. Results: For patients with cancer at all sites, the PCV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the PCA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMRCV outweighed the CMRCA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results. Conclusion: CV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Consumption of flavonoids and risk of hormone-related cancers: a systematic review and meta-analysis of observational studies.

BACKGROUND: Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies. METHODS: Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg's/Egger's test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity. RESULTS: All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76-0.94), flavones (OR = 0.85, 95% CI: 0.77-0.95) and isoflavones (OR = 0.87, 95% CI: 0.82-0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02-1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03-1.50) and flavanones (OR = 1.31, 95% CI: 1.09-1.57). CONCLUSIONS: The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent. TRIAL REGISTRATION: This protocol has been registered on PROSPERO with registration number CRD42020200720 .

Effect of estradiol as a continuous variable on breast cancer survival by menopausal status: a cohort study in China.

High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR 1.79, 95% CI 1.17-2.75, P = 0.008) and OS in post-menopausal women (HR 1.35, 95% CI 1.04-1.74, P = 0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation ("L-shaped" and "U-shaped", respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a "U-shaped" relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

Comparison of outcomes between immediate implantbased and autologous reconstruction: 15-year, single-center experience in a propensity score-matched Chinese cohort.

OBJECTIVE: The number of immediate breast reconstruction (IBR) procedures has been increasing in China. This study aimed to investigate the oncological safety of IBR, and to compare the survival and surgical outcomes between implant-based and autologous reconstruction. METHODS: Data from patients diagnosed with invasive breast cancer who underwent immediate total breast reconstruction between 2001 and 2016 were retrospectively reviewed. Long-term breast cancer-specific survival (BCSS), disease-free survival (DFS), and locoregional recurrence-free survival (LRFS) were evaluated. Patient satisfaction with the breast was compared between the implant-based and autologous groups. BCSS, DFS, and LRFS were compared between groups after propensity score matching (PSM). RESULTS: A total of 784 IBR procedures were identified, of which 584 were performed on patients with invasive breast cancer (implant-based, n = 288; autologous, n = 296). With a median follow-up of 71.3 months, the 10-year estimates of BCSS, DFS, and LRFS were 88.9% [95% confidence interval (CI) (85.1%-93.0%)], 79.6% [95% CI (74.7%-84.8%)], and 94.0% [95% CI (90.3%-97.8%)], respectively. A total of 124 patients completed the Breast-Q questionnaire, and no statistically significant differences were noted between groups (P = 0.823). After PSM with 27 variables, no statistically significant differences in BCSS, DFS, and LRFS were found between the implant-based (n = 177) and autologous (n = 177) groups. Further stratification according to staging, histological grade, lymph node status, and lymph-venous invasion status revealed no significant survival differences between groups. CONCLUSIONS: Both immediate implant-based and autologous reconstruction were reasonable choices with similar long-term oncological outcomes and patient-reported satisfaction among patients with invasive breast cancer in China.

Community-based lung cancer screening by low-dose computed tomography in China: First round results and a meta-analysis.

OBJECTIVE: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis. METHODS: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies. RESULTS: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively. CONCLUSIONS: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.

Development and evaluation of the screening performance of a low-cost high-risk screening strategy for breast cancer.

OBJECTIVE: To develop and evaluate the screening performance of a low-cost high-risk screening strategy for breast cancer in low resource areas. METHODS: Based on the Multi-modality Independent Screening Trial, 6 questionnaire-based risk factors of breast cancer (age at menarche, age at menopause, age at first live birth, oral contraceptive, obesity, family history of breast cancer) were used to determine the women with high risk of breast cancer. The screening performance of clinical breast examination (CBE), breast ultrasonography (BUS), and mammography (MAM) were calculated and compared to determine the optimal screening method for these high risk women. RESULTS: A total of 94 breast cancers were detected among 31,720 asymptomatic Chinese women aged 45-65 years. Due to significantly higher detection rates (DRs) and suitable coverage of the population, high risk women were defined as those with any of 6 risk factors. Among high risk women, the DR for BUS [3.09/1,000 (33/10,694)] was similar to that for MAM [3.18/1,000 (34/10,696)], while it was significantly higher than that for the CBE [1.73/1,000 (19/10,959), P = 0.002]. Compared with MAM, BUS showed significantly higher specificity [98.64% (10,501/10,646) vs. 98.06% (10,443/10,650), P = 0.001], but no significant differences in sensitivity [68.75% (33/48) vs. 73.91% (34/46)], positive prediction values [18.54% (33/178) vs. 14.11% (34/241)], and negative prediction values [99.86% (10,501/10,516) vs. 99.89% (10,443/10,455)]. Further analyses showed no significant difference in the percentages of early stage breast cancer [53.57% (15/28) vs. 50.00% (15/30)], lymph node involvement [22.73% (5/22) vs. 28.00% (7/25)], and tumor size ≥ 2 cm [37.04% (10/27) vs. 29.03% (9/31)] between BUS and MAM. Subgroup analyses stratified by breast densities or age at enrollment showed similar results. CONCLUSIONS: The low-cost high-risk screening strategy based on 6 questionnaire-based risk factors was an easy-to-use method to identify women with high risk of breast cancer. Moreover, BUS and MAM had comparable screening performances among high risk women.

Utility of Preoperative Inflammatory Markers to Distinguish Epithelial Ovarian Cancer from Benign Ovarian Masses.

Background: Inflammatory markers have been reported to be predictors for the presence of epithelial ovarian cancer (EOC), however, the cut-off value of each marker remains unclear and predictive capability of the markers in different histology types of EOC is still unknown. Methods: A total of 207 patients with benign ovarian masses and 887 EOC patients who underwent surgical resection, and were pathologically diagnosed were included. We compared the difference of preoperative inflammatory markers between benign ovarian masses and EOC patients. Stratified analysis by histology subtype was further conducted. Logistic regression analyses and receiver operating characteristic (ROC) curves was used to evaluate the predictive capability of the markers. Results: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were significantly associated with all stages and subtypes of EOC (P<0.001). The optimal cut-off points based on ROC curve analyses for NLR, PLR, and LMR were found to be 2.139 (AUC=0.749, P<0.001), 182.698 (AUC=0.730, P<0.001), and 3.619 (AUC = 0.709, P<0.001), respectively. In low CA125 level patients, high level of NLR and PLR increase the risk of endometrioid EOC, while low level of LMR were significantly associated with an increased risk of serous EOC. Conclusions: In addition to CA125, NLR, PLR, and LMR could be used as predictors of EOC and preoperative inflammatory markers may be used as a potential biomarker for predicting different histotypes of EOC.