Cost-effectiveness analysis of radiotherapy versus surgery for esophageal squamous cell carcinoma in China: a Markov model study based on real-world data.

There are currently limited real-world data on the effectiveness and safety of first-line pembrolizumab combined with chemotherapy in patients with advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in China. This study was conducted to address this knowledge gap. This multicenter retrospective cohort study was conducted at 17 hospitals in China and included adults (⩾18 years) with stage IV primary ESCC, or recurring 6 months after radical radiotherapy/surgery-based combination therapy, who had received first-line pembrolizumab plus chemotherapy. Data were collected from electronic medical records. Endpoints included objective response rate (ORR), disease control rate (DCR) progression-free survival (PFS), overall survival (OS), and safety. Subgroup analyses were conducted to identify patient characteristics and treatment patterns associated with treatment response. In total, 202 patients who had received treatment from 2018 to 2023 were included: 125 (61.9%) newly diagnosed and 77 (38.1%) with recurrence, 181 (89.1%) were male. Pembrolizumab was most commonly combined with paclitaxel + platinum (69.8%) or fluorouracil + platinum (19.3%). After a median follow-up of 22.6 months (95% confidence interval (CI) 20.1-25.4), the ORR and DCR were 60.9% and 87.6% and the median PFS and OS were 10.8 months (95% CI 9.1-13.5) and 17.3 months (95% CI 14.9-19.9), respectively. OS was similar in patients with treatment-naïve and recurrent disease. Among the combination chemotherapy regimens, paclitaxel + platinum was associated with the longest median OS (18.2 months, 95% CI 16.1-22.5). Favorable survival outcomes were observed in patients with oligometastases. No new safety signals were observed. These real-world data indicate that the first-line treatment with pembrolizumab plus chemotherapy is effective and safe in Chinese patients with advanced ESCC and show that paclitaxel + platinum is the most commonly used and most effective partner chemotherapy in China.

First-line treatment with tislelizumab plus chemotherapy has shown clinical benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (OSCC) in China, while its economic burden is unknown. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy from the perspective of the Chinese healthcare system. We constructed a partitioned survival model to compare the cost-effectiveness of tislelizumab plus chemotherapy with chemotherapy in patients with advanced OSCC. Patient characteristics and clinical outcomes were extracted from RATIONALE-306. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were selected as the study outcomes. Sensitivity analysis and subgroup analysis were conducted to test the stability of the results. Tislelizumab plus chemotherapy provided additional 0.48 QALYs with the incremental cost of $16,587.2 than chemotherapy, of which ICER was $34,699.72 per QALY. When the willingness-to-pay threshold was set as $37,260, the novel therapy had a probability of 77% to be cost-effective. Our base-case analysis results were sensitive to utilities of progression-free survival and progression of disease. Our subgroup analysis showed that the novel therapy was associated with cost-effectiveness in patients with a high expression of PD-L1. Tislelizumab plus chemotherapy was likely to be more cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of the Chinese healthcare system. Our findings can provide clinicians and decision-makers with evidence of the cost-effectiveness of tislelizumab.

In China, more than 80% of the esophageal cancer occurs in farmer village, and most of the esophageal cancer patients die at village home. Therefore, the cause of death for esophageal cancer patients has not been well characterized. The present study was thus undertaken to determine the causes of death in patients with esophageal squamous cell carcinoma (ESCC) to provide more information for further prevention and accurate treatment after ESCC diagnosed. All the 8,838 ESCC patients with a detailed cause of death in this study were derived from the ESCC database (1973-2015) in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, China. All the patients were categorized by age (<50 years and≥50 years), gender (male and female) and pathological stage (early, middle and later stage). Chi-Square test was used to analyze the differences in different groups. The results demonstrated that, of the 8,838 died ESCC patients, there were 5,713 males (64.6%) with a mean age of 60.95±9.43 and 3,125 females (35.4%) with a mean age of 61.95±9.47. Notably, 69.5% of the patients died within five years after diagnosis, and the 1-, 3- and 5-year death after diagnosis for these died ESCC patients were 1622 (18.4%), 2960 (33.5%) and 1557 (17.6%), respectively. Overall, the major cause of death for ESCC was due to ESCC recurrence and metastasis (8500, 96.1%), and followed by cardiovascular disease (121, 1.4%), different infections (68, 0.8%), second cancer (52, 0.6%), accident (25, 0.3%), suicide (22, 0.2%), and uncertain cause (50, 0.6%). Furthermore, the major cause of death in males and females was similar (p>0.05) and the cause of death by ESCC recurrence and metastasis, cardiovascular disease, different infections, second cancer, accident, suicide and uncertain cause was 96% (5485) 1.5% (84), 0.8% (44), 0.6% (34), 0.3% (18), 0.2% (16), 0.6% (32), respectively in males and 96.5% (3015), 1.1% (37), 0.8% (24) 0.6% (18), 0.2% (7), 0.2% (6) and 0.6% (18), respectively in females. The present results demonstrate that recurrence and metastasis are the major cause of death both in male and female for ESCC (96%). It is noteworthy that there are 0.2 percent of the ESCC patients have suicide which call for more attention of psychotherapy on cancer patients. [Supported by the Science and Technology Major Projects of Henan Province of China (161100311300), and Correspondence to: Li Dong Wang, the National Key Research and Development Program of China and Correspondence to: Li Dong Wang. Email: ldwang2007@126.com] Note: This abstract was not presented at the meeting. Citation Format: Xiang Yang Zhang, Jian Po Wang, Rui Ping Xu, Ya Qin Hou, Xiu Jian Chen, Ai Li Li, Xi Chen, Shuang Yin Han, Wei Xing Zhao, Li Sun, Min Wang, Wen Ting Fu, Li Dong Wang. Analysis of causes of death in patients with esophageal squamous cell carcinoma in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3273. doi:10.1158/1538-7445.AM2017-3273

Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis. Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.

Background: China has one of the highest incidence rates of oesophageal cancer in the world. The role of human papillomavirus (HPV) has been extensively researched in oesophageal squamous cell carcinoma (OSCC) with indeterminate results. The majority of these studies have been conducted in the Chinese population. Evidence for a definitive HPV-OSCC association could potentially support prophylactic vaccination in target populations, highlighting the need for ongoing investigation. The aim of this review is to summarise the findings of HPV DNA in OSCC tissue in Chinese subjects, with a view to informing further research in this area. Methods: A systematic literature search of the Chinese National Knowledge Infrastructure (CNKI) database, Medline, Embase and PubMed was conducted for all studies in English and Chinese language, examining OSCC tissue for HPV DNA in China. Reference lists of retrieved articles were reviewed and hand searches of relevant, key journals were conducted, to source articles which were not electronically indexed. Sixty-four studies met our selection criteria. Data from case-control and cross-sectional studies were analysed separately for any HPV-OSCC association, using the Epi InfoTM 3.5.3 software program. Results: From all studies conducted in the Chinese population, 2166/5953 (36%) of all OSCC tissue and 478/1684 (28%) of healthy control tissue, tested positive for HPV. We found that 11/16 case-control and cross-sectional studies had a statistically significant crude odds ratio, which supported a potential HPV-OSCC association. The largest study, carried out in the high incidence County of Anyang in Henan Province, reported 207/265 (78%) OSCC tissues testing positive for HPV DNA against 203/357 (57%) controls and had an unadjusted odds ratio of 2.71 (p-value < 0.0001). Conclusion: A rigorous meta-analysis would improve interpretation of the data and a well-designed large-scale case-control study is warranted. If a link is found between HPV and OSCC, prophylactic HPV vaccines could be of significant benefit in China.

Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence. Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up: 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline. No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/ sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use. and alcohol use. Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC.

The striking 3-4:1 male predominance of esophageal squamous cell carcinoma (ESCC) has not yet been well explained. Our hypothesis is that the changes in level of estrogen and/or subtype of estrogen receptor (ER) may exert a protective factor in esophageal carcinogenesis and prognosis of ESCC. Radioimmunoassay (RIA) was used to determine the serum level of estradiol in healthy cohort from high-incidence area (HIA) and low-incidence area (LIA) for esophageal cancer as well as patients with ESCC from HIA in Henan, northern China. The ERβ expression profiling during the multi-stage progression of ESCC pathogenesis was evaluated by immunohistochemistry (IHC). Both males and females from HIA had significant decreases of serum estradiol in high-risk subjects predisposing for ESCC compared to healthy counterparts from LIA (P < 0.01). Furthermore, patients with ESCC from HIA developed the lowest level of estradiol (P < 0.01). ERβ expressed in precursor lesions of ESCC and changed quantitatively and qualitatively with disease progression during the multi-stages process of esophageal carcinogenesis. High frequency of ERβ expression was correlated with less aggressive potential of clinical behavior (P = 0.012, 0.015 for lymph node metastasis and tumor stage, respectively). This study indicates that lower serum level of estradiol may represent higher predisposition for development of ESCC, and ERβ expression and/or nuclear location may predict better outcome for patients with ESCC. The present results provide clues to explain the striking gender difference for ESCC, which warrants further investigations on potential applications of estrogen or analogs in prevention of ESCC.

The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

Background The incidence of esophageal squamous cell carcinoma in China ranks first in the world. The early diagnosis technology is underdeveloped, and the prognosis is poor, which seriously threatens the quality of life of the Chinese people. Epidemiological findings are related to factors such as diet, living habits, and age. The specific mechanism is not clear yet. Metabolomics is a kind of omics that simultaneously and quantitatively analyzes the comprehensive profile of metabolites in living systems. It has unique advantages in the study of the diagnosis and pathogenesis of tumor-related diseases, especially in the search for biomarkers. Therefore, it is desirable to perform metabolic profiling analysis of cancer tissues through metabolomics to find potential biomarkers for the diagnosis and treatment of esophageal squamous cell carcinoma. Methods HPLC-TOF-MS/MS technology and Illumina Hiseq Xten Sequencing was used for the analysis of 210 pairs of matched esophageal squamous cell carcinoma tissues and normal tissues in Zhenjiang City, Jiangsu Province, a high-incidence area of esophageal cancer in China. Bioinformatics analysis was also performed. Results Through metabolomic and transcriptomic analysis, this study found that a total of 269 differential metabolites were obtained in esophageal squamous cell carcinoma and normal tissues, and 48 differential metabolic pathways were obtained through KEGG enrichment analysis. After further screening and identification, 12 metabolites with potential biomarkers to differentiate esophageal squamous cell carcinoma from normal tissues were obtained. Conclusions From the metabolomic data, 4 unknown compounds were found to be abnormally expressed in esophageal squamous cell carcinoma for the first time, such as 9,10-epoxy-12,15-octadecadienoate; 3 metabolites were found in multiple abnormal expression in another tumor, but upregulation or downregulation was found for the first time in esophageal cancer, such as oleoyl glycine; at the same time, it was further confirmed that five metabolites were abnormally expressed in esophageal squamous cell carcinoma, which was similar to the results of other studies, such as PE.

Highly sensitive detection platform-based diagnosis of oesophageal squamous cell carcinoma in China: a multicentre, case–control, diagnostic study

ObjectiveThe purpose of this cost-effectiveness analysis was to estimate the effects of adding camrelizumab to standard chemotherapy as the first-line treatment in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) on health and economic outcomes in China.MethodsA Markov model was developed to simulate the clinical course of typical patients with advanced or metastatic ESCC in the ESCORT-1st trial. Weibull survival model was employed to fit the Kaplan-Meier progression-free survival and overall survival probabilities of the camrelizumab-chemotherapy and placebo-chemotherapy strategy, respectively. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were estimated over a 5-year lifetime horizon. Meanwhile, one-way and probabilistic sensitivity analyses were conducted to test the uncertainty in the model.ResultsOn baseline analysis, the incremental effectiveness and cost of camrelizumab-chemotherapy versus placebo-chemotherapy were 0.15 QALYs and $7,110.56, resulting in an ICER of $46,671.10/QALY, higher than the willingness-to-pay (WTP) threshold of China ($31,498.70/QALY). The results were sensitive to the utility of PFS and cost of camrelizumab.ConclusionThe findings from the present analysis suggest that the addition of camrelizumab to chemotherapy might not be cost-effective in patients with advanced or metastatic ESCC in China.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China, and this neoplasm is associated with high morbidity and mortality as well as clear geographical heterogeneity. Since primary prevention for ESCC lacks a clear intervention target, secondary prevention, also known as screening and early diagnosis and early treatment, has become the mainstay of ESCC prevention and control in China. ESCC screening in China has been subject to decades of evaluation and practice. However, the ESCC screening strategy currently adopted in China has encountered a developmental bottleneck. In this review, we have summarized studies and significant findings for ESCC screening and proposed advancement of screening strategies as follows: 1) evidence from randomized controlled trials is needed to support the effectiveness and health economic value of endoscopic screening for ESCC; 2) the current traditional screening and surveillance strategies warrant reform, and a risk-prediction-based precision strategy should be established; and 3) a deeper understanding of the value of opportunistic screening in the prevention and control of ESCC in China is called for. Due to the low absolute prevalence of precancerous lesions, substantial investment of resources and nonnegligible risks of invasive screening techniques, precision and individualization should be the main direction of cancer screening programs for the future. We advocate cooperation on the part of Chinese scientists to solve this major China-specific health problem in the next decades.

Certain regions of China have high rates of esophageal squamous cell carcinoma (ESCC). Previous studies of human papillomavirus (HPV), a proposed causal factor, have produced highly variable results. We attempted to evaluate HPV and ESCC more definitively using extreme care to prevent DNA contamination. We collected tissue and serum in China from 272 histopathologically-confirmed ESCC cases with rigorous attention to good molecular biology technique. We tested for HPV DNA in fresh-frozen tumor tissue using PCR with PGMY L1 consensus primers and HPV16 and 18 type-specific E6 and E7 primers, and in formalin-fixed paraffin-embedded tumor tissue using SPF(10) L1 primers. In HPV-positive cases, we evaluated p16(INK4a) overexpression and HPV E6/E7 seropositivity as evidence of carcinogenic HPV activity. beta-globin, and thus DNA, was adequate in 98.2% of the frozen tumor tissues (267/272). Of these, 99.6% (95% confidence interval (CI) = 97.9-100.0%) were negative for HPV DNA by PGMY, and 100% (95% CI = 98.6-100%) were negative by HPV16/18 E6/E7 PCR. In the corresponding formalin-fixed paraffin-embedded tumor specimens, 99.3% (95% CI = 97.3-99.9%) were HPV negative by SPF(10). By PGMY, 1 case tested weakly positive for HPV89, a noncancer causing HPV type. By SPF(10), 2 cases tested weakly positive: 1 for HPV16 and 1 for HPV31. No HPV DNA-positive case had evidence of HPV oncogene activity as measured by p16(INK4a) overexpression or E6/E7 seropositivity. This study provides the most definitive evidence to date that HPV is not involved in ESCC carcinogenesis in China. HPV DNA contamination cannot be ruled out as an explanation for high HPV prevalence in ESCC tissue studies with less stringent tissue procurement and processing protocols.

Tumor Location Does Not Impact Long-Term Survival in Patients With Operable Thoracic Esophageal Squamous Cell Carcinoma in China

(1) Background: China has the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 129 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 19 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene-environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.