Spatial consistency of co-exposure to air and surface water pollution and cancer in China.

Humans can be exposed to multiple pollutants in the air and surface water. These environments are non-static, trans-boundary and correlated, creating a complex network, and significant challenges for research on environmental hazards, especially in real-world cancer research. This article reports on a large study (377 million people in 30 provinces of China) that evaluated the combined impact of air and surface water pollution on cancer. We formulate a spatial evaluation system and a common grading scale for co-pollution measurement, and validate assumptions that air and surface water environments are spatially connected and that cancers of different types tend to cluster in areas where these environments are poorer. We observe "dose-response" relationships in both the number of affected cancer types and the cancer incidence with an increase in degree of co-pollution. We estimate that 62,847 (7.4%) new cases of cancer registered in China in 2016 were attributable to air and surface water pollution, and the majority (69.7%) of these excess cases occurred in areas with the highest level of co-pollution. The findings clearly show that the environment cannot be considered as a set of separate entities. They also support the development of policies for cooperative environmental governance and disease prevention.

Reinforcement learning for individualized lung cancer screening schedules: A nested case-control study.

BACKGROUND: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. PURPOSE: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models. METHODS: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). RESULTS: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. CONCLUSIONS: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

The aldehyde dehydrogenase ALDH1B1 exerts antiviral effects through the aggregation of the adaptor MAVS.

Type I interferons (IFNs) are produced by almost all cell types and play a vital role in host defense against viral infection. Infection with an RNA virus activates receptors such as RIG-I, resulting in the recruitment of the adaptor protein MAVS to the RIG-I-like receptor (RLR) signalosome and the formation of prion-like functional aggregates of MAVS, which leads to IFN-ß production. Here, we identified the aldehyde dehydrogenase 1B1 (ALDH1B1) as a previously uncharacterized IFN-stimulated gene (ISG) product with critical roles in the antiviral response. Knockout of ALDH1B1 increased, whereas overexpression of ALDH1B1 restricted, the replication of RNA viruses, such as vesicular stomatitis virus (VSV), Zika virus (ZIKV), dengue virus (DENV), and influenza A virus (IAV). We found that ALDH1B1 localized to mitochondria, where it interacted with the transmembrane domain of MAVS to promote MAVS aggregation. ALDH1B1 was recruited to MAVS aggregates. In addition, ALDH1B1 also enhanced the interaction between activated RIG-I and MAVS, thus increasing IFN-ß production and the antiviral response. Furthermore, Aldh1b1-/- mice developed more severe symptoms than did wild-type mice upon IAV infection. Together, these data identify an aldehyde dehydrogenase in mitochondria that functionally regulates MAVS-mediated signaling and the antiviral response.

Development and validation of an interpretable Markov-embedded multilabel model for predicting risks of multiple postoperative complications among surgical inpatients: a multicenter prospective cohort study.

BACKGROUND: When they encounter various highly related postoperative complications, existing risk evaluation tools that focus on single or any complications are inadequate in clinical practice. This seriously hinders complication management because of the lack of a quantitative basis. An interpretable multilabel model framework that predicts multiple complications simultaneously is urgently needed. MATERIALS AND METHODS: The authors included 50 325 inpatients from a large multicenter cohort (2014-2017). The authors separated patients from one hospital for external validation and randomly split the remaining patients into training and internal validation sets. A MARKov-EmbeDded (MARKED) multilabel model was proposed, and three models were trained for comparison: binary relevance, a fully connected network (FULLNET), and a deep neural network. Performance was mainly evaluated using the area under the receiver operating characteristic curve (AUC). The authors interpreted the model using Shapley Additive Explanations. Complication-specific risk and risk source inference were provided at the individual level. RESULTS: There were 26 292, 6574, and 17 459 inpatients in the training, internal validation, and external validation sets, respectively. For the external validation set, MARKED achieved the highest average AUC (0.818, 95% CI: 0.771-0.864) across eight outcomes [compared with binary relevance, 0.799 (0.748-0.849), FULLNET, 0.806 (0.756-0.856), and deep neural network, 0.815 (0.765-0.866)]. Specifically, the AUCs of MARKED were above 0.9 for cardiac complications [0.927 (0.894-0.960)], neurological complications [0.905 (0.870-0.941)], and mortality [0.902 (0.867-0.937)]. Serum albumin, surgical specialties, emergency case, American Society of Anesthesiologists score, age, and sex were the six most important preoperative variables. The interaction between complications contributed more than the preoperative variables, and formed a hierarchical chain of risk factors, mild complications, and severe complications. CONCLUSION: The authors demonstrated the advantage of MARKED in terms of performance and interpretability. The authors expect that the identification of high-risk patients and the inference of the risk source for specific complications will be valuable for clinical decision-making.

[Surgical Safety of Elderly Hospitalized Patients Stratified by Age in General Surgery].

Objective To compare the surgical safety of elderly hospitalized patients in different age groups undergoing general surgery,and provide references for preoperative evaluation and treatment decision-making.Methods The inpatients ≥ 60 years old in the department of general surgery were selected from a national multi-center survey conducted from January to June in 2015 and from January to June in 2016.The patient characteristics and postoperative outcomes were described,and the risk factors for adverse postoperative outcomes of patients in different age groups were explored.Results The elderly patients (≥75 years old) accounted for 17.33%.The non-elderly patient (< 75 years old) group and the elderly patient (≥75 years old) group had significant differences in the proportions of patients with three or more chronical diseases (13.18% vs.5.36%,P<0.001),emergency surgery (16.64% vs.7.62%,P<0.001),American Society of Anesthesiologists score≥3 (48.68% vs.27.28%,P<0.001),and postoperative return to the intensive care unit(33.64% vs.12.00%,P<0.001).The occurrence of postoperative infectious complications showed no significant difference between the two age groups (7.29% vs.6.40%,P=0.410),while severe complications differed between the two groups (6.51% vs.2.60%,P<0.001).Besides,emergency surgery was a common independent risk factor for the two age groups.Conclusions Advanced age is not a contraindication to surgery of elderly patients.With consideration to patient's physical conditions and available surgical resources,elderly patients can still benefit from surgery.

Prediction of complications associated with general surgery using a Bayesian network.

BACKGROUND: Numerous attempts have been made to identify risk factors for surgery complications, but few studies have identified accurate methods of predicting complex outcomes involving multiple complications. METHODS: We performed a prospective cohort study of general surgical inpatients who attended 4 regionally representative hospitals in China from January to June 2015 and January to June 2016. The risk factors were identified using logistic regression. A Bayesian network model, consisting of directed arcs and nodes, was used to analyze the relationships between risk factors and complications. Probability ratios for complications for a given node state relative to the baseline probability were calculated to quantify the potential effects of risk factors on complications or of complications on other complications. RESULTS: We recruited 19,223 participants and identified 21 nodes, representing 9 risk factors and 12 complications, and 55 direct relationships between these. Respiratory failure was at the center of the network, directly affected by 5 risk factors, and directly affected 7 complications. Cardiopulmonary resuscitation and sepsis or septic shock also directly affected death. The area under the receiver operating characteristic curve for the ability of the network to predict complications was >0.7. Notably, the probability of other severe complications or death significantly increased when a severe complication occurred. Most importantly, there was a 141-fold higher risk of death when cardiopulmonary resuscitation was required. CONCLUSION: We have created a Bayesian network that displays how risk factors affect complications and their interrelationships and permits the accurate prediction of complications and the creation of appropriate preventive guidelines.

Network prediction of surgical complication clusters: a prospective multicenter cohort study.

Complicated relationships exist in both occurrence and progression of surgical complications, which are difficult to account for using a separate quantitative method such as prediction or grading. Data of 51,030 surgical inpatients were collected from four academic/teaching hospitals in a prospective cohort study in China. The relationship between preoperative factors, 22 common complications, and death was analyzed. With input from 54 senior clinicians and following a Bayesian network approach, a complication grading, cluster-visualization, and prediction (GCP) system was designed to model pathways between grades of complication and preoperative risk factor clusters. In the GCP system, there were 11 nodes representing six grades of complication and five preoperative risk factor clusters, and 32 arcs representing a direct association. Several critical targets were pinpointed on the pathway. Malnourished status was a fundamental cause widely associated (7/32 arcs) with other risk factor clusters and complications. American Society of Anesthesiologists (ASA) score ⩾3 was directly dependent on all other risk factor clusters and influenced all severe complications. Grade III complications (mainly pneumonia) were directly dependent on 4/5 risk factor clusters and affected all other grades of complication. Irrespective of grade, complication occurrence was more likely to increase the risk of other grades of complication than risk factor clusters.

Construction and evaluation of networks among multiple postoperative complications.

BACKGROUND AND OBJECTIVE: Postoperative complications confer an increased risk of reoperation, prolonged length of hospital stay, and increased mortality. Many studies have attempted to identify the complex associations among complications to preemptively interrupt their progression, but few studies have looked at complications as a whole to reveal and quantify their possible trajectories of progression. The main objective of this study was to construct and quantify the association network among multiple postoperative complications from a comprehensive perspective to elucidate the possible evolution trajectories. METHODS: In this study, a Bayesian network model was proposed to analyze the associations among 15 complications. Prior evidence and score-based hill-climbing algorithms were used to build the structure. The severity of complications was graded according to their connection to death, with the association between them quantified using conditional probabilities. The data of surgical inpatients used in this study were collected from four regionally representative academic/teaching hospitals in a prospective cohort study in China. RESULTS: In the network obtained, 15 nodes represented complications or death, and 35 arcs with arrows represented the directly dependent relationship between them. With three grades classified on that basis, the correlation coefficients of complications within grades increased with increased grade, ranging from -0.11 to -0.06, 0.16, and 0.21 to 0.4 in grade 1 to grade 3, respectively. Moreover, the probability of each complication in the network increased with the occurrence of any other complication, even mild complications. Most seriously, once cardiac arrest requiring cardiopulmonary resuscitation occurs, the probability of death will be up to 88.1%. CONCLUSIONS: The present evolving network can facilitate the identification of strong associations among specific complications and provides a basis for the development of targeted measures to prevent further deterioration in high-risk patients.

Smoking-related cancer death among men and women in an ageing society (China 2020-2040): a population-based modelling study.

BACKGROUND: China is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications. METHODS: We developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020-2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time. RESULTS: In a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%-50.5%; women: 2.6%-2.1% during 2002-2018), the smoking-related cancer mortality rate with population ageing during 2020-2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35-64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040. CONCLUSIONS: Coordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

Generating real-world evidence compatible with evidence from randomized controlled trials: a novel observational study design applicable to surgical transfusion research.

BACKGROUND: Numerous observational studies have revealed an increased risk of death and complications with transfusion, but this observation has not been confirmed in randomized controlled trials (RCTs). The "transfusion kills patients" paradox persists in real-world observational studies despite application of analytic methods such as propensity-score matching. We propose a new design to address this long-term existing issue, which if left unresolved, will be deleterious to the healthy generation of evidence that supports optimized transfusion practice. METHODS: In the new design, we stress three aspects for reconciling observational studies and RCTs on transfusion safety: (1) re-definition of the study population according to a stable hemoglobin range (gray zone of transfusion decision; 7.5-9.5 g/dL in this study); (2) selection of comparison groups according to a trigger value (last hemoglobin measurement before transfusion; nadir during hospital stay for control); (3) dealing with patient heterogeneity according to standardized mean difference (SMD) values. We applied the new design to hospitalized older patients (aged ≥60 years) undergoing general surgery at four academic/teaching hospitals. Four datasets were analyzed: a base population before (Base Match-) and after (Base Match+) propensity-score matching to simulate previous observational studies; a study population before (Study Match-) and after (Study Match+) propensity-score matching to demonstrate effects of our design. RESULTS: Of 6141 older patients, 662 (10.78%) were transfused and showed high heterogeneity compared with those not receiving transfusion, particularly regarding preoperative hemoglobin (mean: 11.0 vs. 13.5 g/dL) and intraoperative bleeding (≥500 mL: 37.9% vs. 2.1%). Patient heterogeneity was reduced with the new design; SMD of the two variables was reduced from approximately 100% (Base Match-) to 0% (Study Match+). Transfusion was related to a higher risk of death and complications in Base Match- (odds ratio [OR], 95% confidence interval [CI]: 2.68, 1.86-3.86) and Base Match+ (2.24, 1.43-3.49), but not in Study Match- (0.77, 0.32-1.86) or Study Match+ (0.66, 0.23-1.89). CONCLUSIONS: We show how choice of study population and analysis could affect real-world study findings. Our results following the new design are in accordance with relevant RCTs, highlighting its value in accelerating the pace of transfusion evidence generation and generalization.

Nationwide gastric cancer prevention in China, 2021-2035: a decision analysis on effect, affordability and cost-effectiveness optimisation.

OBJECTIVE: To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness. DESIGN: Using a cohort of Chinese men and women born during 1951-1980, we assumed that different prevention strategies were conducted, including eradication of Helicobacter pylori (Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021-2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention. RESULTS: During 2021-2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%-35.5% and 6.9%-44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%-49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening, CONCLUSION: Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.

Quantifying lung cancer heterogeneity using novel CT features: a cross-institute study.

BACKGROUND: Radiomics-based image metrics are not used in the clinic despite the rapidly growing literature. We selected eight promising radiomic features and validated their value in decoding lung cancer heterogeneity. METHODS: CT images of 236 lung cancer patients were obtained from three different institutes, whereupon radiomic features were extracted according to a standardized procedure. The predictive value for patient long-term prognosis and association with routinely used semantic, genetic (e.g., epidermal growth factor receptor (EGFR)), and histopathological cancer profiles were validated. Feature measurement reproducibility was assessed. RESULTS: All eight selected features were robust across repeat scans (intraclass coefficient range: 0.81-0.99), and were associated with at least one of the cancer profiles: prognostic, semantic, genetic, and histopathological. For instance, "kurtosis" had a high predictive value of early death (AUC at first year: 0.70-0.75 in two independent cohorts), negative association with histopathological grade (Spearman's r: - 0.30), and altered expression levels regarding EGFR mutation and semantic characteristics (solid intensity, spiculated shape, juxtapleural location, and pleura tag; all p < 0.05). Combined as a radiomic score, the features had a higher area under curve for predicting 5-year survival (train: 0.855, test: 0.780, external validation: 0.760) than routine characteristics (0.733, 0.622, 0.613, respectively), and a better capability in patient death risk stratification (hazard ratio: 5.828, 95% confidence interval: 2.915-11.561) than histopathological staging and grading. CONCLUSIONS: We highlighted the clinical value of radiomic features. Following confirmation, these features may change the way in which we approach CT imaging and improve the individualized care of lung cancer patients.

Effects of population aging on the mortality burden of related cancers in urban and rural areas of China, 2004-2017: a population-based study.

OBJECTIVE: China is a developing country with urban-rural disparities and accelerating population aging. Therefore, quantifying the effects of population aging on the cancer mortality burden is urgently needed. METHODS: Using data from China's death surveillance datasets (2004-2017), we decomposed and quantified the effects of population aging and factor variations on cancer mortality rates in urban and rural China during 2004-2017 through a decomposition method. R ratios were used to assess the extent of the mortality decreases attributable to factor variations offsetting the increases attributable to population aging for 4 aging-related cancers (lung, colorectal, esophageal, and stomach cancer). RESULTS: Overall, population aging has led to continued increases in cancer mortality rates in China during 2004-2017 (mortality rates attributable to population aging: 8.63/100,000 for urban men, 4.21/100,000 for urban women, 11.95/100,000 for rural men, and 5.66/100,000 for rural women). The 4 cancers displayed 3 patterns. The mortality rates from lung cancer in rural China and from colorectal cancer nationwide increased because of both population aging and factor variations. Population aging was primarily responsible for the growing mortality due to lung cancer in urban areas. However, for esophageal and stomach cancer, the effect of population aging was not dominant, thus resulting in decreases in mortality rates. CONCLUSIONS: Health resource allocation should prioritize areas or cancers more adversely affected by population aging. The burden of cancer will continue to increase in the future, because of rapid population aging, but can still be offset or even reversed with enhanced cancer control and prevention.

[Patterns of Perioperative Blood Transfusion in Patients with Blood Loss during Major Cardiac Surgery].

Objective To investigate the patterns of perioperative blood transfusion in patients with blood loss during major cardiac surgery,so as to provide data reference for rational and standardized blood use.Methods The adult patients(aged 18 years or above)who underwent vascular surgery,coronary artery bypass grafting surgery,heart valve surgery or surgery for congenital heart disease in a national multicenter(four large hospitals)survey in China,2015-2016 were included in this study.We described their baseline characteristics,postoperative outcomes,and in particular,bleeding and patterns of perioperative blood transfusion(autologous and allogeneic,the latter including red blood cells,plasma,and platelet,or a combination of these components).Results Autologous blood transfusion in operation accounted for the highest proportion(58.84%)in patients undergoing heart valve surgery.The patients undergoing vascular surgery had the largest autologous blood transfusion volume(722 ml)and the highest intraoperative transfusion proportion of allogeneic blood(53.28%),especially that of platelet(39.34%).Compared with the transfusion of red blood cells,the transfusion of other blood components showed concentrated time distribution,and the proportion of plasma transfusion was the highest one day post operation.With the increase in bleeding volume,combined transfusion presented increased proportion and became the dominant transfusion pattern.Conclusions The blood transfusion patterns varied significantly depending on different types of cardiac surgery,different perioperative stages,and different bleeding volumes.It is necessary to formulate the targeted transfusion practice scheme on the basis of understanding the current situation,so as to make better use of blood resources and improve the safety of transfusion.

Expanding restrictive transfusion evidence in surgical practice: a multicentre, prospective cohort study.

BACKGROUND: Findings of observational studies investigating the impact of transfusions are at odds with those of randomised controlled trials, raising concern that observational studies may be inappropriate to inform transfusion decisions. We examined whether observational data could replicate evidence from randomised controlled trials on restrictive transfusion in cardiac and orthopaedic surgery, and be generalised to broader specialties as well as to a lower haemoglobin transfusion threshold (7 g/dL). MATERIAL AND METHODS: A multicentre, prospective cohort study was performed at three representative regional hospitals in China between 2015 and 2016. Participants were surgical inpatients (≥18 years; hospital stay ≥24 h) in six specialties: cardiac, cerebral, vascular (CCV), and orthopaedic, general, thoracic (non-CCV). Patients with a stable haemoglobin (7-10 g/dL) constituted the primary analytic sample, while patients with ≥500 mL intra-operative bleeding were analysed separately to avoid haemoglobin instability. The association of transfusion with surgical outcomes (death, in-hospital complications) was evaluated. RESULTS: The transfusion rate was 10.7% in 36,607 patients (mean age, 52.5±14.3 years; 52.3% female). After restriction, stratification, and propensity score matching to reduce patients' heterogeneity, transfusion was unrelated to death (CCV: odds ratio [OR]=0.74, 95% confidence interval [CI]: 0.16-3.39; non-CCV: OR 0.83, 95% CI: 0.36-1.94) and the composite complication (CCV: OR 1.31, 95% CI: 0.63-2.72; non-CCV: OR=1.24, 95% CI: 0.81-1.90). The results were consistent in subgroups (elderly, coronary heart disease, malignant tumour, severe illness) and applicable to patients with significant bleeding after restoration of a stable haemoglobin. DISCUSSION: Transfusion at a stable haemoglobin concentration of 7-10 g/dL did not alter surgical outcomes. Our results show the feasibility of observational data to expand restrictive transfusion to broader specialties and a lower transfusion threshold in surgical practice.

Optimizing the timing of diagnostic testing after positive findings in lung cancer screening: a proof of concept radiomics study.

BACKGROUND: The timeliness of diagnostic testing after positive screening remains suboptimal because of limited evidence and methodology, leading to delayed diagnosis of lung cancer and over-examination. We propose a radiomics approach to assist with planning of the diagnostic testing interval in lung cancer screening. METHODS: From an institute-based lung cancer screening cohort, we retrospectively selected 92 patients with pulmonary nodules with diameters ≥ 3 mm at baseline (61 confirmed as lung cancer by histopathology; 31 confirmed cancer-free). Four groups of region-of-interest-based radiomic features (n = 310) were extracted for quantitative characterization of the nodules, and eight features were proven to be predictive of cancer diagnosis, noise-robust, phenotype-related, and non-redundant. A radiomics biomarker was then built with the random survival forest method. The patients with nodules were divided into low-, middle- and high-risk subgroups by two biomarker cutoffs that optimized time-dependent sensitivity and specificity for decisions about diagnostic workup within 3 months and about repeat screening after 12 months, respectively. A radiomics-based follow-up schedule was then proposed. Its performance was visually assessed with a time-to-diagnosis plot and benchmarked against lung RADS and four other guideline protocols. RESULTS: The radiomics biomarker had a high time-dependent area under the curve value (95% CI) for predicting lung cancer diagnosis within 12 months; training: 0.928 (0.844, 0.972), test: 0.888 (0.766, 0.975); the performance was robust in extensive cross-validations. The time-to-diagnosis distributions differed significantly between the three patient subgroups, p < 0.001: 96.2% of high-risk patients (n = 26) were diagnosed within 10 months after baseline screen, whereas 95.8% of low-risk patients (n = 24) remained cancer-free by the end of the study. Compared with the five existing protocols, the proposed follow-up schedule performed best at securing timely lung cancer diagnosis (delayed diagnosis rate: < 5%) and at sparing patients with cancer-free nodules from unnecessary repeat screenings and examinations (false recommendation rate: 0%). CONCLUSIONS: Timely management of screening-detected pulmonary nodules can be substantially improved with a radiomics approach. This proof-of-concept study's results should be further validated in large programs.

Global evolution of research on pulmonary nodules: a bibliometric analysis.

Aim: To provide a historical and global picture of research concerning lung nodules, compare the contributions of major countries and explore research trends over the past 10 years. Methods: A bibliometric analysis of publications from Scopus (1970-2020) and Web of Science (2011-2020). Results: Publications about pulmonary nodules showed an enormous growth trend from 1970 to 2020. There is a high level of collaboration among the 20 most productive countries and regions, with the USA located at the center of the collaboration network. The keywords 'deep learning', 'artificial intelligence' and 'machine learning' are current hotspots. Conclusions: Abundant research has focused on pulmonary nodules. Deep learning is emerging as a promising tool for lung cancer diagnosis and management.

Predictions of mortality related to four major cancers in China, 2020 to 2030.

BACKGROUND: Cancer has become a global health problem, and assessments of cancer mortality are important for effective public health policy-making and adequate resource allocation. In this study, we aimed to predict the mortality rates and numbers of deaths related to four common cancers (lung, liver, stomach, and esophagus) in China from 2020 to 2030 and to estimate the corresponding cancer burden caused by population aging and tobacco smoking. METHODS: Cancer mortality data (2004-2017) were extracted from China's death surveillance datasets, and China's population figures (2020-2030) were obtained from the United Nations population projections. Smoking prevalence data were retrieved from a World Health Organization global report, and relative risks of smoking and cancers were derived from large-scale Asian studies. We predicted the deaths related to the four major cancers and age-standardized mortality rates using joinpoint regression and linear regression models. The tobacco smoking-related burden of these four major cancers was estimated using the population attributable fraction. RESULTS: Unlike lung cancer mortality which was predicted to continue to increase, the age-standardized mortality rates for digestive cancers (liver, stomach, and esophageal cancers) are predicted to decline over the next decade. The number of deaths caused by the four major cancers is predicted to increase from 1,490,304 in 2020 to 1,823,960 in 2030. The age-specific mortality rates of the four major cancers are predicted to increase with age after 40-45 years, peaking in the age groups of 80-84 and ≥85 years. In 2030, the combined number of deaths from the four examined cancers among adults aged ≥65 years is predicted to be 1,167,153, accounting for 64% of all deaths from these cancers. Tobacco smoking is predicted to contribute to nearly 29% of deaths from these cancers, corresponding to 527,577 deaths. CONCLUSIONS: The overall trend in the combined total mortality from four major cancers is predicted to decline over the next decade; however, the corresponding death toll is expected to surge, in the context of China's population aging and high smoking prevalence. These estimates provide data-driven evidence for China to implement effective cancer control measures in the future.