Cost-Effectiveness Analysis of Risk Factor-Based Lung Cancer Screening Program by Low-Dose Computer Tomography in Current Smokers in China.

Although the effectiveness of lung cancer screening by low-dose computed tomography (LDCT) could be shown in China, there could be variation in the evidence concerning the economic impact. Our study explores the cost-effectiveness of lung cancer screening and optimizes the best definition of a high-risk population. A Markov model consisting of the natural history and post-diagnosis states was constructed to estimate the costs and quality-adjusted life years (QALYs) of LDCT screening compared with no screening. A total of 36 distinct risk factor-based screening strategies were assessed by incorporating starting ages of 40, 45, 50, 55, 60 and 65 years, stopping ages of 69, 74 and 79 years as well as smoking eligibility criteria. Screening data came from community-based mass screening with LDCT for lung cancer in Guangzhou. Compared with no screening, all screening scenarios led to incremental costs and QALYs. When the willingness-to-pay (WTP) threshold was USD37,653, three times the gross domestic product (GDP) per capita in China, six of nine strategies on the efficiency frontier may be cost-effective. Annual screening between 55 and 79 years of age for those who smoked more than 20 pack-years, which yielded an incremental cost-effectiveness ratio (ICER) of USD35,000.00 per QALY gained, was considered optimal. In sensitivity analyses, the result was stable in most cases. The trends of the results are roughly the same in scenario analyses. According to the WTP threshold of different regions, the optimal screening strategies were annual screening for those who smoked more than 20 pack-years, between 50 and 79 years of age in Zhejiang province, 55-79 years in Guangdong province and 65-74 years in Yunnan province. However, annual screening was unlikely to be cost-effective in Heilongjiang province under our modelling assumptions, indicating that tailored screening policies should be made regionally according to the local epidemiological and economic situation.

Accurate classification of pulmonary nodules by a combined model of clinical, imaging, and cell-free DNA methylation biomarkers: a model development and external validation study.

BACKGROUND: There is an unmet clinical need for accurate non-invasive tests to facilitate the early diagnosis of lung cancer. We propose a combined model of clinical, imaging, and cell-free DNA methylation biomarkers that aims to improve the classification of pulmonary nodules. METHODS: We conducted a prospective specimen collection and retrospective masked evaluation study. We recruited participants with a solitary pulmonary nodule sized 5-30 mm from 24 hospitals across 20 cities in China. Participants who were aged 18 years or older and had been referred with 5-30 mm non-calcified and solitary pulmonary nodules, including solid nodules, part solid nodules, and pure ground-glass nodules, were included. We developed a combined clinical and imaging biomarkers (CIBM) model by machine learning for the classification of malignant and benign pulmonary nodules in a cohort (n=839) and validated it in two cohorts (n=258 in the first cohort and n=283 in the second cohort). We then integrated the CIBM model with our previously established circulating tumour DNA methylation model (PulmoSeek) to create a new combined model, PulmoSeek Plus (n=258), and verified it in an independent cohort (n=283). The clinical utility of the models was evaluated using decision curve analysis. A low cutoff (0·65) for high sensitivity and a high cutoff (0·89) for high specificity were applied simultaneously to stratify pulmonary nodules into low-risk, medium-risk, and high-risk groups. The primary outcome was the diagnostic performance of the CIBM, PulmoSeek, and PulmoSeek Plus models. Participants in this study were drawn from two prospective clinical studies that were registered (NCT03181490 and NCT03651986), the first of which was completed, and the second of which is ongoing because 25% of participants have not yet finished the required 3-year follow-up. FINDINGS: We recruited a total of 1380 participants. 1097 participants were enrolled from July 7, 2017, to Feb 12, 2019; 839 participants were used for the CIBM model training set, and the rest (n=258) for the first CIBM validation set and the PulmoSeek Plus training set. 283 participants were enrolled from Oct 26, 2018, to March 20, 2020, as an independent validation set for the PulmoSeek Plus model and the second validation set for the CIBM model. The CIBM model validation cohorts had area under the curves (AUCs) of 0·85 (95% CI 0·80-0·89) and 0·85 (0·81-0·89). The PulmoSeek Plus model had better discrimination capacity compared with the CIBM and PulmoSeek models with an increase of 0·05 in AUC (PulmoSeek Plus vs CIBM, 95% CI 0·022-0·087, p=0·001; and PulmoSeek Plus vs PulmoSeek, 0·018-0·083, p=0·002). The overall sensitivity of the PulmoSeek Plus model was 0·98 (0·97-0·99) at a fixed specificity of 0·50 for ruling out lung cancer. A high sensitivity of 0·98 (0·96-0·99) was maintained in early-stage lung cancer (stages 0 and I) and 0·99 (0·96-1·00) in 5-10 mm nodules. The decision curve showed that if an invasive intervention, such as surgical resection or biopsy, was deemed necessary at more than the risk threshold score of 0·54, the PulmoSeek Plus model would provide a standardised net benefit of 82·38% (76·06-86·79%), equivalent to correctly identifying approximately 83 of 100 people with lung cancer. Using the PulmoSeek Plus model to classify pulmonary nodules with two cutoffs (0·65 and 0·89) would have reduced 89% (105/118) of unnecessary surgeries and 73% (308/423) of delayed treatments. INTERPRETATION: The PulmoSeek Plus Model combining clinical, imaging, and cell-free DNA methylation biomarkers aids the early diagnosis of pulmonary nodules, with potential application in clinical decision making for the management of pulmonary nodules. FUNDING: The China National Science Foundation, the Key Project of Guangzhou Scientific Research Project, the High-Level University Construction Project of Guangzhou Medical University, the National Key Research & Development Programme, the Guangdong High Level Hospital Construction "Reaching Peak" Plan, the Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, The Leading Projects of Guangzhou Municipal Health Sciences Foundation, the Key Research and Development Plan of Shaanxi Province of China, the Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship, the Scheme of Guangzhou for Leading Team in Innovation, the Guangzhou Development Zone International Science and Technology Cooperation Project, and the Science and Technology Planning Project of Guangzhou.

Real-time assessment of COVID-19 epidemic in Guangdong Province, China using mathematical models.

China government has relaxed the response measures of COVID-19 in early December 2022. In this report, we assessed the number of infections, the number of severe cases based on the current epidemic trend (October 22, 2022 to November 30, 2022) using a transmission dynamics model, called modified susceptible-exposed-infectious-removed (SEIR) to provide valuable information to ensure the medical operation of the healthcare system under the new situation. Our model showed that the present outbreak in Guangdong Province peaked during December 21, 2022 to December 25, 2022 with about 14.98 million new infections (95% CI: 14.23-15.73 million). The cumulative number of infections will reach about 70% of the province's population from December 24, 2022 to December 26, 2022. The number of existing severe cases is expected to peak during January 1, 2023 to January 5, 2023 with a peak number of approximately 101.45 thousand (95% CI: 96.38-106.52 thousand). In addition, the epidemic in Guangzhou which is the capital city of Guangdong Province is expected to have peaked around December 22, 2022 to December 23, 2022 with the number of new infections at the peak being about 2.45 million (95% CI: 2.33-2.57 million). The cumulative number of infected people will reach about 70% of the city's population from December 24, 2022 to December 25, 2022 and the number of existing severe cases is expected to peak around January 4, 2023 to January 6, 2023 with the number of existing severe cases at the peak being about 6.32 thousand (95% CI: 6.00-6.64 thousand). Predicted results enable the government to prepare medically and plan for potential risks in advance.

Ergonomical Assessment of Three-Dimensional Versus Two-Dimensional Thoracoscopic Lobectomy.

In this study. we compared ergonomical domains characteristics of three-dimensional (3D) versus two-dimensional (2D) video-systems in thoracoscopic lobectomy using a scoring-scale-based assessment. Seventy patients (mean age, 69 ± 6.9 years, 43 males and 27 females) with early stage lung cancer were randomized to undergo thoracoscopic lobectomy by either 3D (N = 35) or 2D (N = 35) video-systems. All operations were divided into 5 standardized surgical steps (vein, artery, bronchus, fissure, and lymph nodes), which were evaluated by 4 thoracic surgeons using a scoring scale (score range from 1, unsatisfactory to 3,excellent) entailing assessment of 3 ergonomical domains: exposure, instrumentation and maneuvering. Primary outcome was a difference ≥10% in the maneuvering domain steps. At intergroup comparisons, there was no difference in demographics. The 3D system results were better for maneuvering domain total score and particularly for the artery and bronchus steps scores (score ≥10%, P ≤ 0.006). Other significant differences included exposure of the vein, artery and bronchus (P ≤ 0.03). Results favoring the 2D system included maneuvering, exposure and instrumentation of the fissure (P = 0.001). Inter-rater concordance of ergonomics scoring was satisfactory (Cronbach's α range, 0.85-0.88). Operative time was significantly shorter in the 3D group (127 ± 19 min vs 143±18 min, P = 0.001) whereas there was no difference in hospital stay (3.4 ± 1.2 vs 4.1 ± 1.6 days, P = 0.07). In this study comparison of ergonomic domains scoring in 3D versus 2D thoracoscopic lobectomy favored the 3D system for the maneuvering total score, which proved inversely correlated with operative times possibly due to a better perception of depth and more precise surgical maneuvering.

China lung transplantation developing: past, present and future.

Lung transplantation in China has been developing for almost 40 years (1979-2019). The pioneers of this procedure experienced struggles and obstacles upon accomplishment of the initial 20 cases of lung transplantation. Like the expanding process of transplant programs elsewhere in western countries and other regions in Asia, transplant teams in China have found their own way to step forward, with the establishment of the two largest centers in Beijing and Wuxi. Since 2015, which was a novel start and milestone for transplant affairs in China, the pace of transplant volume and comparable quality of care for lung transplant recipients have increased noticeably. We reviewed the advancement of lung transplantation programs and registry setup in China and indicated that more socioeconomic factors and human care aspects needed to be considered to benefit Chinese recipients, which may further inspire the modification of criteria of listing and organ utilization based on East Asian cultural and traditional origins.

Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

OBJECTIVE: Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments. DESIGN: Literature review, pooling analysis and correlation analysis. DATA SOURCES: PubMed, from 1 January 2010 to 30 June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments. RESULTS: Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29). CONCLUSIONS: No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.

Evaluation bias in objective response rate and disease control rate between blinded independent central review and local assessment: a study-level pooled analysis of phase III randomized control trials in the past seven years.

BACKGROUND: In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. METHODS: Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. RESULTS: A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), P<0.01, I2=11%; exp-DCR: OR=0.90 (0.81-1.01), P=0.07, I2=42%] and control arms [con-ORR: OR=0.79 (0.72-0.85), P<0.01, I2=17%; con-DCR: OR=0.94 (0.86-1.02), P=0.14, I2=12%]. No sign of evaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I2=0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I2=0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). CONCLUSIONS: Blind independent central review remained irreplaceable to monitor local assessment, but its complete-case implementation may be unnecessary.

Long-term outcome and cost-effectiveness of complete versus assisted video-assisted thoracic surgery for non-small cell lung cancer.

BACKGROUND: To compare the outcomes and costs of two methods of video-assisted thoracoscopic surgery (VATS) major pulmonary resection in patients with clinically resectable non-small cell lung cancer (NSCLC). METHODS: Between January 2000 and December 2007, 1,058 patients with proven stages I-IIIA NSCLC underwent complete VATS (c-VATS) or assisted VATS (a-VATS) major pulmonary resection together with a systematic nodal dissection. RESULTS: The study cohort consisted of 736 men and 322 women. Mean operative time was shorter for the a-VATS cohort compared with the c-VATS group (P = 0.038). Overall survival (OS) at 5 years based on Kaplan-Meier analysis was 55.3% (95%CI, 50.6-60.0%) for those who underwent c-VATS and 47.7% (95%CI, 41.2-54.2%) for those who underwent a-VATS (P = 0.404). Gender, final pathology, TNM stage, and pT status were significant predictive factors for OS according to multivariate analysis. The total cost of a-VATS lobectomy was lower than that of c-VATS lobectomy. CONCLUSIONS: c-VATS and a-VATS yield similar results in patients with clinically resectable NSCLC. a-VATS, however, may be less expensive and easier to adopt, making it a particularly attractive option for thoracic surgeons in developing countries.