Performance of Prediction Models for Esophageal Squamous Cell Carcinoma in General Population: A Systematic Review and External Validation Study.

INTRODUCTION: Prediction models for esophageal squamous cell carcinoma (ESCC) need to be proven effective in the target population before they can be applied to population-based endoscopic screening to improve cost-effectiveness. We have systematically reviewed ESCC prediction models applicable to the general population and performed external validation and head-to-head comparisons in a large multicenter prospective cohort including 5 high-risk areas of China (Fei Cheng, Lin Zhou, Ci Xian, Yang Zhong, and Yan Ting). METHODS: Models were identified through a systematic review and validated in a large population-based multicenter prospective cohort that included 89,753 participants aged 40-69 years who underwent their first endoscopic examination between April 2017 and March 2021 and were followed up until December 31, 2022. Model performance in external validation was estimated based on discrimination and calibration. Discrimination was assessed by C-statistic (concordance statistic), and calibration was assessed by calibration plot and Hosmer-Lemeshow test. RESULTS: The systematic review identified 15 prediction models that predicted severe dysplasia and above lesion (SDA) or ESCC in the general population, of which 11 models (4 SDA and 7 ESCC) were externally validated. The C-statistics ranged from 0.67 (95% confidence interval 0.66-0.69) to 0.70 (0.68-0.71) of the SDA models, and the highest was achieved by Liu et al (2020) and Liu et al (2022). The C-statistics ranged from 0.51 (0.48-0.54) to 0.74 (0.71-0.77), and Han et al (2023) had the best discrimination of the ESCC models. Most models were well calibrated after recalibration because the calibration plots coincided with the x = y line. DISCUSSION: Several prediction models showed moderate performance in external validation, and the prediction models may be useful in screening for ESCC. Further research is needed on model optimization, generalization, implementation, and health economic evaluation.

Changes in Geographic Variation and Socioeconomic Inequalities in Esophageal Cancer Mortality in China, 1973-2017.

BACKGROUND: Geographic variability in esophageal cancer has been reported in China, but data are lacking at the local level. We aimed to investigate changes in disparities in esophageal cancer-related mortality among Chinese counties and whether county-level socioeconomic status was associated with this variation. METHODS: We used data from a nationwide survey and population-based cancer registries to calculate esophageal cancer-related mortality rates for 782 Chinese counties for the periods of 1973-1975 and 2015-2017. We performed hotspot analysis to identify spatial clusters. We used a multivariable negative binomial regression model to estimate the associations between county-level socioeconomic factors and mortality. RESULTS: From 1973-1975 to 2015-2017, the age-standardized esophageal cancer-related mortality rate decreased from 27 to 8 per 100,000 person-years in China. By county, 577 (74%) of 782 counties experienced decreasing mortality. Geographic disparities in mortality substantially narrowed, with the gap in mortality rates between 90th and 10th percentile counties decreasing from 55 per 100,000 person-years in 1973-1975 to 16 in 2015-2017. However, clusters of elevated rates persisted across north-central China. Rurality [adjusted mortality rate ratio (MRR) 1.15; 95% confidence interval (CI), 1.10-1.21], per capita gross domestic product (adjusted MRR, 0.95; 95% CI, 0.91-0.98), and percentage of people with a high-school diploma (adjusted MRR, 0.86; 95% CI, 0.84-0.87) in a county were significantly associated esophageal cancer-related mortality rates. CONCLUSIONS: China has made substantial progress in reducing esophageal cancer-related mortality and disparities, but the intercounty differences remain large. IMPACT: Continued efforts are needed to address the geographical and socioeconomic disparities in esophageal cancer.

Years lived with disability of cancer in China: findings from disability weights measurement with a focus on the effect of disease burden.

Disability weights are crucial for quantifying health loss associated with non-fatal outcomes and were not well assessed in different countries, especially for specific cancer. Therefore, this study aimed to identify disability weights with a focus on specific cancer in a large Chinese population. Two types of web surveys were conducted, and 254 health states, including 30 new states for specific cancer, were investigated using paired comparison methods. The years lived with disability (YLDs) of cancer were calculated as the sum of the prevalence of each sequela of cancer multiplied by its relative disability weight. In total, 44,069 participants were eligible for the disability weights study. The disability weights of 254 health states were estimated. Among those, the disability weights of 18 specific cancer types varied greatly at diagnosis and primary treatment stage, with the value ranging from 0.619 (95% uncertainty interval (UI) 0.606-0.632) for brain cancer to 0.167 (95% UI 0.158-0.176) for oropharyngeal cancer. The discrepancy in YLDs calculated by different disability weights was high, and the largest gap for all cancer combined was approximately 30.14%. When calculated using the cancer-specific disability weights, a total of 1,967,830 (95% UI 1,928,880-2,008,060) YLDs of cancer were recorded in China. The disability weights of cancer varied greatly among cancer types and populations, which had considerable influence on the estimation of the disease burden. Cancer-specific disability weights could provide a more accurate evaluation of the cancer burden.

Prevalence and management of pain in lung cancer patients in northern China: A multicenter cross-sectional study.

BACKGROUND: Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross-sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China. METHODS: A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed. RESULTS: A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%). CONCLUSION: Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High-quality pain education for both patients and physicians is needed in the future.

Global, regional and national burden of primary liver cancer by subtype.

INTRODUCTION: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the two main histological subtypes of primary liver cancer. Estimates of the burden of liver cancer by subtype are needed to facilitate development and evaluation of liver cancer control globally. We provide worldwide, regional and national estimates of HCC and iCCA incidence using high-quality data. METHODS: We used population-based cancer registry data on liver cancer cases by histological subtype from 95 countries to compute the sex- and country-specific distributions of HCC, iCCA and other specified histology. Subtype distributions were applied to estimates of total liver cancer cases for 2018 from the Global Cancer Observatory. Age-standardised incidence rates (ASRs) were calculated. RESULTS: There were an estimated 826,000 cases of liver cancer globally in 2018: 661,000 HCC (ASR 7.3 cases per 100,000); 123,000 iCCA (ASR 1.4) and 42,000 other specified histology (ASR 0.5). HCC contributed 80% of the world total liver cancer burden followed by iCCA (14.9%) and other specified histology (5.1%). HCC rates were highest in Eastern Asia (ASR 14.8), Northern Africa (ASR 13.2) and South-Eastern Asia (ASR 9.5). Rates of iCCA were highest in South-Eastern Asia (ASR 2.9), Eastern Asia (ASR 2.0), Northern Europe, the Caribbean and Central America and Oceania (ASR all 1.8). CONCLUSION: We have shown the importance of uncovering the distinct patterns of the major subtypes of liver cancer. The use of these estimates is critical to further develop public health policy to reduce the burden of liver cancer and monitor progress in controlling HCC and iCCA globally.

Estimated Cost-effectiveness of Endoscopic Screening for Upper Gastrointestinal Tract Cancer in High-Risk Areas in China.

Importance: Upper gastrointestinal tract cancer, including esophageal and gastric cancers, in China accounts for 50% of the global burden. Endoscopic screening may be associated with a decreased incidence of and mortality from upper gastrointestinal tract cancer. Objective: To evaluate the cost-effectiveness of endoscopic screening for esophageal and gastric cancers among people aged 40 to 69 years in areas of China where the risk of these cancers is high. Design, Setting, and Participants: For this economic evaluation, a Markov model was constructed for initial screening at different ages from a health care system perspective, and 5 endoscopic screening strategies with different frequencies (once per lifetime and every 10 years, 5 years, 3 years, and 2 years) were evaluated. The study was conducted between January 1, 2019, and October 31, 2020. Model parameters were estimated based on this project, government documents, and published literature. For each initial screening age (40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a closed cohort of 100 000 participants was assumed to enter the model and follow the alternative strategies. Main Outcomes and Measures: Cost-effectiveness was measured by calculating the incremental cost-effectiveness ratio (ICER), and the willingness-to-pay threshold was assumed to be 3 times the per capita gross domestic product in China (US $10 276). Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of model findings. Results: The study included a hypothetical cohort of 100 000 individuals aged 40 to 69 years. All 5 screening strategies were associated with improved effectiveness by 1087 to 10 362 quality-adjusted life-years (QALYs) and increased costs by US $3 299 000 to $22 826 000 compared with no screening over a lifetime, leading to ICERs of US $1343 to $3035 per QALY. Screening at a higher frequency was associated with an increase in QALYs and costs; ICERs for higher frequency screening compared with the next-lower frequency screening were between US $1087 and $4511 per QALY. Screening every 2 years would be the most cost-effective strategy, with probabilities of 90% to 98% at 3 times the per capita gross domestic product of China. The model was the most sensitive to utility scores of esophageal cancer- or gastric cancer-related health states and compliance with screening. Conclusions and Relevance: The findings suggest that combined endoscopic screening for esophageal and gastric cancers may be cost-effective in areas of China where the risk of these cancers is high; screening every 2 years would be the optimal strategy. These data may be useful for development of policies targeting the prevention and control of upper gastrointestinal tract cancer in China.

Health-related quality of life in patients with esophageal cancer or precancerous lesions assessed by EQ-5D: A multicenter cross-sectional study.

BACKGROUND: We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health-related quality of life (HRQoL). METHODS: A hospital-based multicenter cross-sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life-5 dimension (EQ-5D-3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ-5D utility scores. RESULTS: A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self-reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ-5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ-5D utility scores of EC patients. CONCLUSIONS: There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost-utility analysis in populations in China.

The long-term population impact of endoscopic screening programmes on disease burdens of gastric cancer in China: A mathematical modelling study.

BACKGROUND: Gastric cancer (GC) incidence and mortality in China remained high due to delayed diagnosis and accounted for about half of the world's GC cases and deaths. Early detection with endoscopic screening and consequent timely treatment can significantly improve survival. This study aimed to explore the long-term population impact of endoscopic screening on national GC disease burdens in China. METHODS: Most of previous studies investigated the disease burdens of cancer using Markov model or age-period-cohort (APC) model, which are difficult to estimate the population size of undiagnosed cases. In this paper, we proposed a new dynamic compartmental model based on GC natural history and calibrated model outputs to diagnosed GC cases and GC-related death counts using Markov Chain Monte Carlo methods. We investigated the impact of screening strategies with various coverage (10%, 40%, 70%) and frequency (every 1, 3, 5 years) on disease burdens. RESULTS: We estimated that 2.22 (95%CI: 1.97-2.47) million Chinese are living with GC in 2019, among which, 42.7% (40.3-45.0%) remained undiagnosed. Without systematic screening, we projected 10.46 (9.07-11.86) million incident cases and 7.35 (6.59-8.11) million GC-related deaths over the next 30 years (2019-2049). Screening with coverage rate at 10%, 40%, 70% every 3 years could prevent 0.85 (0.63-1.06), 2.32 (1.79-2.86), and 3.04 (2.38-3.70) million incident cases, and prevent 1.17 (1.01-1.32), 3.08 (2.70-3.46), and 3.93 (3.46-4.40) million deaths respectively, compared with 'no screening' scenario. Screening would substantially increase the number of diagnosed GC cases within the first three years of program initiation, but this number would quickly reduce below 'no screening' scenario. Three-yearly screening at the above coverage rates would reduce the proportion of undiagnosed GC cases to 38.8% (36.9-40.7%), 25.5% (23.4-27.6%), and 17.8% (16.0-19.6%) by 2049, respectively. Delaying implementation of the screening program would substantially reduce its effectiveness. CONCLUSIONS: Initiating national endoscopic screening programmes would likely have a major effect on reducing GC incidence and mortality in China. Health resources should be substantially increased and directed to treatment of GC to cope with the initial rise in diagnosed GC cases.

Annual cost of illness of stomach and esophageal cancer patients in urban and rural areas in China: A multi-center study.

OBJECTIVE: Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereas there were few studies on the financial burden of the two cancers. METHODS: Costs per hospitalization of all patients with stomach or esophageal cancer discharged between September 2015 and August 2016 in seven cities/counties in China were collected, together with their demographic information and clinical details. Former patients in the same hospitals were sampled to collect information on annual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost was obtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness (ACI) was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost, stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalization were itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars (1 USD=6.6423 RMB). RESULTS: Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urban patients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancer patients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACI was associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries. Western medicine fee took the largest proportion of cost per hospitalization. CONCLUSIONS: The ACI of stomach and esophageal cancer was tremendous and varied substantially among the population in China. Preferential policies of medical insurance should be designed to tackle with this burden and further reduce the health care inequalities.

[Cost-effectiveness analysis of esophageal cancer once-in-a-lifetime endoscopic screening in high-risk areas of rural China].

OBJECTIVE: To estimate the cost-effectiveness of esophageal cancer endoscopic screening once-in-a-lifetime and to predict the optimal screening age for people in high-risk areas of rural China. METHODS: A Markov model was constructed to predict and compare the effect of four esophageal cancer endoscopic screening modalities which varied with different screening ages. Long-term epidemiological effectiveness and cost-effectiveness were predicted by simulation of the model. RESULTS: Compared with the control group, strategies starting at 40, 45, 50 and 55 year-old had saved life-years of 629.51, 769.88, 738.98 and 533.21 years per 100 000 people, respectively, of which the strategy starting at 45 year-old saved the maximum life years. All strategies were cost-effective and starting at 40 year-old cost the most per life-year saved. Among all alternatives, strategies starting age at 45 year-old and 50 year-old were incremental cost-effective, and the incremental cost-effective ratios were 34 962.87 and 3 346.43 RMB per life year saved, respectively. CONCLUSIONS: The strategy starting at 40 year-old implemented at present and other strategies were cost-effective in high-risk areas of rural China. However, the 45-year-old group is more aligned with the principle of cost-effectiveness. Considering the cost-effectiveness of different strategies and social economic status, 45 year-old is regarded as the optimal starting age of esophageal cancer once-in-a-lifetime endoscopic screening and is recommended in areas lacking health resources. The strategy of starting age at 40 year-old which could obtain better screening effects would be preferable in wealthy regions.

Cost-benefit analysis of esophageal cancer endoscopic screening in high-risk areas of China.

AIM: To estimate the cost-benefit of endoscopic screening strategies of esophageal cancer (EC) in high-risk areas of China. METHODS: Markov model-based analyses were conducted to compare the net present values (NPVs) and the benefit-cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied according to the targeted screening age, screening frequencies, and follow-up intervals. Model parameters were collected from population-based studies in China, published literatures, and surveillance data. RESULTS: Compared with non-screening outcomes, all strategies with hypothetical 100,000 subjects saved life years. Among five dominant strategies determined by the incremental cost-effectiveness analysis, screening once at age 50 years incurred the lowest NPV (international dollar-I$55 million) and BCR (2.52). Screening six times between 40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy, screening thrice between 40-70 years at a 10-year interval resulted in relatively lower NPV, but the same BCR. CONCLUSION: EC endoscopic screening is cost-beneficial in high-risk areas of China. Policy-makers should consider the cost-benefit, population acceptance, and local economic status when choosing suitable screening strategies.

Cost-benefit analysis of screening for esophageal and gastric cardiac cancer.

In 2005, a program named "Early Detection and Early Treatment of Esophageal and Cardiac Cancer" (EDETEC) was initiated in China. A total of 8279 residents aged 40-69 years old were recruited into the EDETEC program in Linzhou of Henan Province between 2005 and 2008. Howerer, the cost-benefit of the EDETEC program is not very clear yet. We conducted herein a cost-benefit analysis of screening for esophageal and cardiac cancer. The assessed costs of the EDETEC program included screening costs for each subject, as well as direct and indirect treatment costs for esophageal and cardiac severe dysplasia and cancer detected by screening. The assessed benefits of this program included the saved treatment costs, both direct and indirect, on esophageal and cardiac cancer, as well as the value of prolonged life due to screening, as determined by the human capital approach. The results showed the screening cost of finding esophageal and cardiac severe dysplasia or cancer ranged from RMB 2707 to RMB 4512, and the total cost on screening and treatment was RMB 13 115-14 920. The cost benefit was RMB 58 944-155 110 (the saved treatment cost, RMB 17 730, plus the value of prolonged life, RMB 41 214-137 380). The ratio of benefit-to-cost (BCR) was 3.95-11.83. Our results suggest that EDETEC has a high benefit-to-cost ratio in China and could be instituted into high risk areas of China.

[Economic evaluation of "early detection and treatment of esophageal cancer"].

BACKGROUND & OBJECTIVE: In China, esophageal cancer is the forth death cause of malignant cancers. The survival rate of esophageal cancer patients is less than 10%. Early detection and treatment of esophageal cancer is essential to improve the survival rate of these patients. This study was to evaluate the economic and social benefits of the project "early detection and treatment of esophageal cancer" through cost-benefit analysis, so as to provide evidence to extend this project. METHODS: Interview with structured questionnaires was conducted by stratified sampling among 136 esophageal cancer patients in 3 hospitals at Linzhou City, and a sampling survey was conducted among 53 patients at their homes afterwards. The 2 surveys measured the expense of "traditional treatment of esophageal cancer". Based on an intervention study of "early detection and treatment of esophageal cancer" among 936 persons at Linzhou City, cost-benefit analysis and the evaluation of economic burden of disease among esophageal cancer patients were carried out. RESULTS: The expense of "traditional treatment of esophageal cancer" was 7,183 Yuan per patient. Regarding the 936 persons who were recruited to the intervention study, the cost was 148,246 Yuan, and the benefit was 589,006 Yuan. The difference between benefit and cost of the project was 440,760 Yuan. The benefit-cost ratio was 4:1. By the project, the ratio of the expense in treating disease to the total family income in 1 year was reduced from 1.300 to 0.125. CONCLUSION: The cost of "early detection and treatment of esophageal cancer" is low, while the benefit is high, and the project can also lighten the economic burden of esophageal cancer patients.