Cost-Effectiveness Analysis of Chemoradiotherapy Compared to Surgery in Patients with Stage I Esophageal Squamous Cell Carcinoma in Japan

Cost-Effectiveness Analysis of Chemoradiotherapy Compared to Surgery in Patients with Stage I Esophageal Squamous Cell Carcinoma in Japan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-Effectiveness Analysis of Chemoradiotherapy Compared to Surgery in Patients with Stage I Esophageal Squamous Cell Carcinoma in Japan Takuro Ariga, Kensuke Moriwaki, Kousuke Morimoto, Katsuyuki Sakanaka, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8915993/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Purpose We performed a model-based cost-effectiveness analysis of the use of surgical treatment (ST) versus chemoradiotherapy (CRT) for stage I esophageal cancer in Japan. Materials and Methods A model for partitioned survival analysis was developed to estimate the long-term medical costs and quality-adjusted life years (QALYs) for patients who had received either ST or CRT. Data on survival times were taken from the JCOG0502 trial. Utility values were estimated by applying a mapping algorithm based on Japanese data from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire. From the perspective of public healthcare, only direct medical costs were considered. A discount rate of 2% per year was applied to long-term costs and QALYs to estimate the incremental cost-effectiveness ratio (ICER) of CRT compared to ST. Results The incremental cost of CRT versus ST was estimated to be $ 26,313 (USD), the incremental QALY was 0.630, and the ICER was $ 41,742/QALY. Sensitivity analysis showed that the parameter with a relatively large effect on the ICER was the utility weight of progressive disease with esophagus preserved patients in CRT. The variations in ICERs ranged from approximately $ 37,113/QALY to $ 47,690/QALY. With willingness-to-pay thresholds ranging from $ 50,000/QALY to $ 100,000/QALY, CRT was more cost-effective than ST, with the probability of being cost-effective estimated to range from 59.3% to 76.3%. Conclusions In Japan, CRT for stage I esophageal cancer may be more cost-effective than ST, if the acceptable ICER is $ 50,000/QALY. Esophageal cancer Cost-effective analysis QOL ICER chemoradiotherapy. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction According to the Japanese cancer statistics published by the National Cancer Center [ 1 , 2 ], the incidence of esophageal cancer in Japan in 2019 was 20.9 cancers per 100,000 people, and the mortality was 8.9 deaths per 100,000 people. According to the data from the National Esophageal Cancer Registry of the Japanese Esophageal Cancer Association [ 3 ], the proportion of stage I (TNM 8th Edition [ 4 ]) patients is the highest incidence rate, accounting for 39.2%. The JCOG0502 study [ 5 ] by the Japan Clinical Oncology Group (JCOG) compared esophagectomy and chemoradiotherapy (CRT) for stage I esophageal squamous cell carcinoma. Results of this study showed that the overall survival (OS) rates of patients treated with CRT were non-inferior compared with surgical treatment (ST) (hazard ratio [HR] 1.052 [95% confidence interval [CI]: 0.674–1.640]), however, ST obtained a longer progression-free survival (PFS) (HR: 1.478 [95% CI: 1.01–2.16]). Therefore, the Japanese Guidelines for Esophageal Cancer (GL2022) [ 6 , 7 ] suggest considering ST but also recommend CRT followed by appropriate monitoring and salvage therapy for patients who wish to preserve their esophagus. In addition to OS and PFS, health-related quality of life (HRQOL) must be considered when choosing treatment modalities. There have been a few published reports on HRQOL of patients with esophageal cancer who underwent ST or CRT [ 8 – 10 ]. Ariga et al [ 8 ]. showed that patients undergoing CRT had significantly better HRQOL than ST, while Chen et al [ 9 ]. concluded that ST was better HRQOL than CRT for some of the Quality-of-Life Questionnaire (QLQ)-C30 items. Sunde et al [ 10 ]. concluded that the advantages of ST and CRT varied depending on survey item in QLQs. Therefore, the HRQOL evaluations of patients with early esophageal cancer receiving ST vs CRT remain uncertain. Furthermore, evaluations from a health economics perspective have become increasingly important in recent years. Since the 1990s, health technology assessments (HTAs) and approaches to decision-making on healthcare policy have been adopted by various countries, which have used them to determine whether drugs and medical technologies can be reimbursed by public insurance and set prices [ 11 ]. In 2021, the development of Japanese medical practice guidelines [ 12 ] included a section on evaluating health economic. Health economic evaluations of the treatments for esophageal cancer have been performed by other countries [ 13 – 15 ], but there is no the cost-effectiveness of CRT compared with ST for stage I esophageal cancer based on the Japanese insurance system. Therefore, we analyzed the cost-effectiveness and HRQOL of ST versus CRT for esophageal cancer, aiming to support treatment planning and guide healthcare policy. Materials and Method Model-based cost-effectiveness analysis A partitioned survival analysis model (PartSA) was used to assess the cost-effectiveness of CRT compared with ST. The patients who underwent ST were stratified into 3 statuses as follows: “progression-free survival (PFS) after esophagectomy", "survival with progressive disease (PD) after esophagectomy", and "death" (Fig. 1 ). Since patients who underwent CRT could survive with the esophagus preserved, the patients were stratified into 4 statuses as follows: "PFS with esophagus preserved", "PD with esophagus preserved", "PD after esophagectomy", and "death" (Fig. 1 ). These models were used to predict long-term medical costs, duration of survival, and quality-adjusted life years (QALY) for both the ST and CRT patients. Utility weights and cost per cycle were parameterized for each stratified patient statuses. For this analysis, parametric survival values were fitted to the Kaplan-Meier survival curves of patients in the JCOG0502 [ 5 ] that were based on esophagectomy-free survival (EFS), PFS, and OS. The parameters on the EFS, PFS, and OS Kaplan-Meyer graphs were then used to calculate changes over time in the proportions of surviving patients. The proportions and expected costs and QALYs for each stratified statuses were calculated to obtain the incremental cost-effectiveness ratio (ICER) of CRT compared to ST. ICER was expressed as "incremental cost divided by QALY", and this represents the additional cost required for the CRT patients to gain 1 QALY greater than the ST patients. Although there is no explicit threshold for ICER regarding cancer treatments in Japan, the Central Social Insurance Medical Council's cost-effectiveness evaluation system operate if estimated ICERs for treating a fatal disease such as cancer range from $ 50,000 to $ 75,000/QALY (at $ 1 = 150 yen, 7.5 to 11.25 million yen/QALY), from $ 75,000 to $ 100,000/QALY (11.25 to 15 million yen/QALY), and greater than $ 100,000/QALY (15 million yen/QALY ), the adjusted portion of the official price is adjusted downward by 30%, 60% and 90% respectively. For this reason, these price adjustment thresholds were also used in this study as reference values for socially acceptable values of ICER. The period of analysis (time horizon) was set at 40 years, and the discount rate of 2% per year was applied to the long-term costs and benefits, as based on the national cost-effectiveness evaluation guidelines. The cycle length of the model was set at one month. TreeAge Pro Healthcare 2022 was used to construct and simulate the model. Ethical review was not applicable because all data used for the model and analysis were obtained from existing databases or published papers. Parameter settings Survival curves The PartSA model was used to extrapolate the EFS, PFS, and OS for each treatment group. Recently, Guyot et al [ 16 ]. proposed a method to construct data on patient survival times data from images of Kaplan-Meier curves and number at-risk information by simulation. The procedure they used was as follows: data from graphs showing time vs. probability of cumulative survival times were extracted from images of Kaplan-Meier curves. Then, based on the plot data and the number at risk reported in the clinical trials, they created patient datasets. In this study, we used the Kaplan-Meier EFS, PFS, and OS curves from the JCOG0502 [ 5 ] and fit several parametric functions to create patient datasets. We used WebPlotDigitizer (Version 4.6) to extract plot information. R (version 4.2.0) and R studio (2022.02.2 Build 485) were also used to create patient datasets. To select the optimal function, we referred to the good visual fit to the Kaplan-Meier curves of the JCOG0502 [ 5 ], and the metrics provided by the Akaike Information Criterion and Bayesian Information Criterion, which express the degree of fit. As a result, the Weibull function was judged to be the best fit, and we used this function to perform calculations in the basic analysis. We estimated outcomes by extrapolating the OS of CRT group to that of the ST group, assuming similar OS rates for both groups. When PFS and EFS intersected with OS in the long-term extrapolation, we estimated outcomes by substituting OS values for PFS and EFS in subsequent years. Costs In this model, only direct medical costs were considered from the perspective of Japanese public medical payers, and the following cost parameters were established: i) treatment cost of ST group (/patient), ii) medical cost for PFS after esophagectomy in the ST group (/month), iii) medical cost for PD after esophagectomy in the ST group (/month), iv) treatment cost of CRT group (/patient), v) medical cost for PFS with esophagus preserved in the CRT group (/month), vi) medical cost for PD with esophagus preserved in the CRT group (/month), vii) medical cost for PD after esophagectomy in the CRT group (/month), and viii) terminal care cost in both group (/patient) (Table 1). Calculations of the above cost parameters were based on the Diagnosis Procedure Combination/Per-Diem Payment System (DPC/PDPS), a Japanese public insurance reimbursement system, and the claims database provided by the Japan Medical Data Center (JMDC) (Table 1). The DPC/PDPS consists of two parts: the comprehensive portion, which pays a fixed fee per diem based on the diagnosis; and the piecework portion, which pays based on the treatments that were performed. The comprehensive component was defined as 33 days for the ST group and 14 days for the CRT group, in accordance with the mean duration of hospitalization as reported in the DPC/PDPS 2024. For the ST group, a continuous hospitalization period was implemented. The surgical fee model was based on an open esophagectomy with three-field lymph node dissection, gastric tube reconstruction, and anesthesia fees. For the CRT group, the radiation fee model was based on the four-field irradiation technique, and 2 cycle chemotherapy comprised seven consecutive days of hospitalization. Outpatient irradiation fees were incorporated into the piecework portion during outpatient visits. The JMDC claims database is Japan's largest privately available epidemiological claims database. It accumulates subscriber registers, receipts (inpatient, outpatient, and prescription), and data from health checkups provided by insurers. The database assigns a unique ID to each subscriber, which allows the tracing of transfers and visits to multiple facilities. However, elderly patients older than 75 years are not included in the JMDC database because of variations in the different insurance medical fee systems in Japan. In this study, during the period from January 2005 to March 2021, we selected for analysis case histories with the standard diagnostic categories that related to esophageal cancer (N = 62,247). The extracted data was processed into a panel format of data over time to simplify the tabulation of changes in medical costs over time. The initial treatment costs in cost parameters i) and iv) were based on the DPC/PDPS 2024. For the follow-up examinations in cost parameters ii) and v), we built models based on the post-treatment survey date by Nakanoko et al [ 17 ] and calculated based on the DPC/PDPS 2024. The pre-death medical expenditures of patients with esophageal cancer showed that the consumption of medical resources increased two months before death, peaked in the month before death, and decreased in the month after death. We defined the total medical cost in the three months before death as cost parameter viii). The JMDC claims database does not explicit the recurrence of cancer. We performed an exploratory simulation of the PartSA model in the base case setting and found that the duration of PD in CRT group was about 23 ~ 24 months. Therefore, we assumed that the two years before the terminal stage (4 ~ 28 months before death) was the period with PD and estimated the cost parameters iii), vi), and vii). In this analysis, the ST and CRT groups were assumed to have the same medical costs for PD and end-of-life care. Utility weights The utility weights for each status were estimated based on published data by Ariga et al [ 8 ]. The mapping algorithm used from EORTC-QLQ30 to EQ-5D-5L that was developed by Hagiwara et al. [ 18 ] was used to transform from EORTC-QLQ30 data to utility weights. Sensitivity analysis In this study, a one-way sensitivity analysis was conducted for the parameter settings in the model, and the results of this sensitivity analysis are summarized in a tornado diagram. To estimate the distribution of probabilities for ICERs and to perform a probabilistic assessment of cost-effectiveness, we performed a probabilistic sensitivity analysis that was based on 1,000 second-order Monte Carlo simulations. We set up probability distributions limited to those parameters of the model for which information on probability distributions as 95% CI. We repeated the calculations of expected cost, expected QALY, and ICER 1,000 times by sampling the input values for each parameter from the established probability distribution. Based on results of second-order Monte-Carlo simulations, we constructed cost-effectiveness acceptability curves. We estimated the proportion of iterations in which CRT would be preferred in terms of cost-effectiveness, assuming willingness-to-pay thresholds of $ 50,000, $ 75,000, and $ 100,000/QALY. Additionally, as mentioned earlier, we extrapolated the OS for CRT OS to the ST group to analyze the base case. To account for the impact of OS differences, we analyzed the ICER when the OS for ST group was adjusted by plus-minus10%, with the OS for CRT group set as HR = 1. Table 1. Parameter settings Estimate SE/ Variability Plausible range Distribution Reference Cost parameter (USD) ST group Cost of esophagectomy including hospitalization (/patient) 20,322 ±10% 18,289 22,354 Triangle EO Medical cost in PFS state after esophagectomy (/month) EO 1st year 138 ±10% 124 151 Triangle 2nd year 123 ±10% 111 136 Triangle 3rd year 76 ±10% 68 83 Triangle 4th year 69 ±10% 62 76 Triangle 5th year 62 ±10% 56 68 Triangle Subsequent year 55 ±10% 49 60 Triangle Medical cost in PD after esophagectomy (/month) 2,033 30 1,973 2,093 Gamma JMDC Terminal care cost (/patient) 12,175 325 11,539 12,812 Gamma JMDC CRT group Cost of CRT including hospitalization (/patient) 7,348 ±10% 6,613 8,083 Triangle EO Medical cost in PFS with esophagus preserved (/month) EO 1st year 328 ±10% 295 361 Triangle 2nd year 219 ±10% 197 241 Triangle 3rd year 171 ±10% 154 188 Triangle 4th year 116 ±10% 105 128 Triangle 5th year 109 ±10% 98 120 Triangle Subsequent year 55 ±10% 49 60 Triangle Medical cost in PD with esophagus preserved (/month) 2,033 30 1,973 2,093 Gamma JMDC Cost of esophagectomy including hospitalization (/patient) 20,322 ±10% 18,289 22,354 Triangle EO Medical cost in PD after esophagectomy (/month) 2,033 30 1,973 2,093 Gamma JMDC Terminal care cost (/patient) 12,175 325 11,539 12,812 Gamma JMDC Utility parameter ST group PFS after esophagectomy 0.843 0.032 0.78 0.906 Beta PD after esophagectomy 0.768 0.032 0.706 0.83 Beta CRT group PFS with esophagus preserved 0.902 0.032 0.84 0.964 Beta PD with esophagus preserved 0.827 0.032 0.765 0.889 Beta PD after esophagectomy 0.799 0.032 0.737 0.861 Beta Discount rate for cost and QALY 0.02 - 0 0.04 - Time horizon (year) 40 - 20 40 - CRT: chemoradiotherapy, EO: expert opinion, JMDC: JMDC claims database, PD: progressive disease, PF: progression-free survival, QALY: quality-adjusted life years, ST: surgical treatment Results Base case analysis The Utility weight for each status was shown in Table 1, and the results of cohort simulation on trends in health status and long-term medical costs for each group are summarized in Fig. 2 and Table 2 . The incremental QALY for the CRT group relative to the ST group was estimated to be 0.630. Although the initial treatment cost was lower in the CRT group, showed that the incremental total medical cost for CRT was $ 26,313 higher than for ST, with the ICER estimated to be $ 41,742/QALY. Table 2 Base case results ST CRT Incremental (vs ST) Life years 15.323 15.323 0.000 Duration of PFS after esophagectomy (year) 14.969 0.000 -14.969 Duration of PFS with esophagus preserved (years) 0.000 13.392 13.392 Duration of PD after esophagectomy (years) 0.354 0.444 0.091 Duration of PD with esophagus preserved (years) 0.000 1.487 1.487 QALY 10.573 11.203 0.630 Total cost (USD) 48,174 74,486 26,313 Initial treatment cost 20,163 7,262 -12,901 Medical cost during PFS after esophagectomy 10,988 0 -10,988 Medical cost during PFS with esophagus preserved 0 16,538 16,538 Medical cost during PD after esophagectomy 8,010 9,669 1,659 Cost of esophagectomy in CRT group 0 1,066 1,066 Medical cost during PD with esophagus preserved 0 30,939 30,939 ICER (USD/QALY gained) 41,742 CRT: chemoradiotherapy, ICER: incremental cost-effectiveness ratio, PD: progressive disease, PFS: progression-free survival, QALY: quality-adjusted life years, ST: surgical treatment Sensitivity analysis The results of the deterministic sensitivity analysis are summarized in Fig. 3 . The parameter that had a relatively large impact on the ICER in CRT was the utility weight of PD with esophagus preserved, and the variation to these parameters was in the range of $ 37,113/QALY to $ 47,690/QALY. The results suggested that ST might dominate CRT, depending on the established utility weights in PFS for the CRT and ST groups, as shown in Table 3 . Table 3 Sensitivity analysis of utility weights Utility weight for PFS with esophagus preserved in CRT group Treatment Cost (USD) Incremental cost (USD) QALY Incremental QALY ICER (USD/QALY) 0.840 ST 48,174 10.573 CRT 74,486 26,313 10.527 -0.046 Dominated 0.871 ST 48,174 10.573 CRT 74,486 26,313 10.865 0.292 90,028 0.902 ST 48,174 10.573 CRT 74,486 26,313 11.203 0.630 41,742 0.933 ST 48,174 10.573 CRT 74,486 26,313 11.541 0.968 27,169 0.964 ST 48,174 10.573 CRT 74,486 26,313 11.879 1.307 20,139 Utility weight for PFS in ST group Treatment Cost (USD) Incremental cost (USD) QALY Incremental QALY ICER (USD/QALY) 0.780 ST 48,174 9.801 CRT 74,486 26,313 11.203 1.402 18,773 0.812 ST 48,174 10.187 CRT 74,486 26,313 11.203 1.016 25,898 0.843 ST 48,174 10.573 CRT 74,486 26,313 11.203 0.630 41,742 0.875 ST 48,174 10.958 CRT 74,486 26,313 11.203 0.245 107,516 0.906 ST 48,174 11.344 CRT 74,486 26,313 11.203 -0.141 Dominated CRT: chemoradiotherapy, PFS: progression-free survival, ICER: incremental cost-effectiveness ratio, QALY: quality-adjusted life years, ST: surgical treatment The results of probabilistic sensitivity analysis are summarized in Fig. 4 . The cost-effectiveness acceptability curve showed that CRT was more cost-effective than ST were estimated to be 59.3%, 67.5%, and 75.8%, when the acceptable values for ICER were $ 50,000, $ 75,000, and $ 100,000/QALY, respectively. The result of sensitivity analysis for OS was summarized in Table 4 and Fig. 5 . It showed that OS for ST group exceeded the lower bound of our ICER when the HR was set as 1.016. Table 4 HR for OS in ST Treatment Cost (USD) Incremental cost (USD) QALY Incremental QALY ICER (USD/QALY) 0.900 ST 46,190 10.029 CRT 74,489 28,299 11.203 1.175 24,094 0.950 ST 47,156 10.306 CRT 74,489 27,333 11.203 0.897 30,470 1.000 ST 48,174 10.573 CRT 74,489 26,315 11.203 0.630 41,744 1.050 ST 49,245 10.829 CRT 74,489 25,244 11.203 0.374 67,502 1.100 ST 50,368 11.076 CRT 74,489 24,121 11.203 0.127 189,508 CRT: chemoradiotherapy, HR: Hazard ratio, ICER: incremental cost-effectiveness ratio, OS: Overall survival, QALY: quality-adjusted life years, ST: surgical treatment Discussion In this study, we compared CRT to ST for stage I esophageal cancer from the perspective of the Japanese public healthcare payer. We estimated that the incremental cost was $ 26,313, the incremental QALY was 0.630, and ICER was $ 41,742/QALY. In Japan, a system was initiated in 2019 to utilize the evidence of cost-effectiveness in the price adjustments of new medical technologies. Under this system, a rule was adopted to adjust the proportion of the calculated price of new medical technologies that corresponded to the additional premium, according to the level of ICER. For the price adjustment of items that required special consideration, three ICER thresholds were established before mentioned. Although technologies other than drugs and medical devices are currently not covered by this system, the minimum acceptable value for ICER is $ 50,0000/QALY, the point estimate-based result of $ 41,742/QALY obtained in this study showed that CRT was superior to ST in terms of cost-effectiveness. Although our sensitivity analysis indicates the superiority of CRT, the results are not robust due to several factors. First, regarding the difference in QALYs between the two groups, several articles [ 19 – 22 ] indicated that patients in the ST group may obtain improved QALYs because of less invasive treatments and the introduce of perioperative adjuvant therapy. Inomata et al [ 19 ]. reported that several studies of minimally invasive esophagectomy indicated that early interventions such as perioperative rehabilitation within the Enhanced Recovery After Surgery framework can reduce various adverse events associated with ST [ 20 – 22 ]. These findings suggest that the comparable significance of the improved QALYs between CRT and ST is not fixed. Additionally, it should be noted that Intensity-Modulated Radiation Therapy (IMRT) is being incorporated into the CRT and is anticipated to enhance QOL by reducing the adverse events. In both groups, the treatment procedures are becoming less invasive, which is likely to affect future estimates on incremental QALYs and ICERs. From a cost perspective, the introduction of IMRT may increase the initial treatment costs for the CRT group [ 23 ] and potentially alter the ICER. We employed a utility analysis developed by Ariga et al [ 8 ]. that was conducted for ethnic groups, treatment techniques, and public insurance similar to those in the JCOG0502 [ 5 ]. However, results of utility analysis of esophageal cancer treatments vary as mentioned [ 9 , 10 ] and these results are inconsistent; therefore, the construction of a model derived from multiple studies has the potential to yield divergent results. In addition, we assumed equivalent OS between the ST and CRT. However, as shown in Table 4 and Fig. 5 , when the OS for ST group was set at HR = 1.016, it exceeded the lower bound of the ICER we defined. If the OS for ST group is slightly better than that for CRT, the ST could potentially be considered more cost-effective. Although this study showed that CRT was superior in cost-effectiveness in this study, ST might be superior in cost-effectiveness influenced by various factors as mentioned above. This indicates that both ST and CRT are equally effective and cost-effective in the Japanese domestic insurance system. Therefore, treatment decisions can be made based on shared decision-making with the patient. The novelty of this study was that it used the JMDC claims database to evaluate the cost-effectiveness of CRT and ST for esophageal cancer. The JMDC claims database is the largest commercial epidemiological receipt database in Japan. Using this database, we were able to estimate ICERs that considered the real-world setting in Japan. It is also significant that we applied the EQ-5D-5L mapping algorithm to the EORTC-QLQ30 data to estimate utility weights that reflected the preferences of the general population in Japan for various health conditions of esophageal cancer patients. Our approaches could be applied to health economic evaluations of patients with other types of cancer. This study has several limitations. At first, the JMDC data only included receipt data and did not provide clinical information on patients, such as stage. Therefore, the analysis could not be limited to stage I patients. The cost of maintenance chemotherapy following CRT for stage II–III patients may be perceived as an additional factor to consider. Second, clinical events such as progression depended on analytical definitions in this study. The analysis utilized surrogate triggers, such as re-initiation of surgery, radiation therapy after surgery, or chemotherapy occurring after completion of the initial therapy. Third, endoscopic treatments and photodynamic therapy could not be included as triggers because of the lack of explicit data. Fourth, the survival probabilities were based on the best visual fit and did not incorporate individual patient data from JCOG0502 [ 5 ]. Therefore, the accuracy of specific survival probabilities may be lower than if individual patient data were used. Fifth, the insurance medical fee in Japan revises every two years, creating uncertainty on cost parameters. In conclusion, CRT for stage I esophageal cancer in Japan is likely to be more cost-effective than ST. Although further investigation of resource consumption, HRQOL, and clinical benefits in Japanese patients is needed, our approach is expected to support clinical and policy decision making. Abbreviations CRT chemoradiotherapy PD progressive disease PFS progression-free survival ST surgical therapy. Declarations Declarations of generative AI and AI-assisted technologies in the manuscript preparation process Funding: This study was supported by a specific grant from the Japanese Society for Radiation Oncology Acknowledgements This manuscript was provided financial support by Japanese Society for Radiation Oncology. The authors are grateful to Prof. Ariga of Iwate Medical University for providing his data set. References Hori M, Matsuda T, Shibata A et al (2015) Cancer incidence and incidence rates in Japan in 2009: A study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 45(9):884–891. 10.1093/jjco/hyv088 Katanoda K, Hori M, Saito E et al (2021) Updated trends in cancer in Japan: Incidence in 1985–2015 and mortality in 1958–2018—a sign of decrease in cancer incidence. J Epidemiol 31(7):426–450. 10.2188/jea.JE20200416 Watanabe M, Toh Y, Ishihara R et al (2023) Comprehensive registry of esophageal cancer in Japan, 2015. Esophagus 20(1):1–28. 10.1007/s10388-022-00950-5 Brierley JD, Gospodarowicz MK (2017) Christian Wittekind. TNM Classification of Malignant Tumours, 8th Edition. New York: Wiley-Blackwell Kato K, Ito Y, Nozaki I et al (2021) Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma. Gastroenterology 161(6):1878–1886e2. 10.1053/j.gastro.2021.08.007 Kitagawa Y, Ishihara R, Ishikawa H et al (2023) Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus 20(3):343–372. 10.1007/s10388-023-00993-2 Kitagawa Y, Ishihara R, Ishikawa H et al (2023) Esophageal cancer practice guidelines 2022 edited by the Japan Esophageal Society: part 2. Esophagus 20(3):373–389. 10.1007/s10388-023-00994-1 Ariga H, Nemoto K, Miyazaki S et al (2009) Prospective Comparison of Surgery Alone and Chemoradiotherapy With Selective Surgery in Resectable Squamous Cell Carcinoma of the Esophagus. Int J Radiat Oncol Biol Phys 75(2):348–356. 10.1016/j.ijrobp.2009.02.086 Chen CY, Hsieh VCR, Chang CH et al (2017) Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients. Dis Esophagus 30(10):1–8. 10.1093/dote/dox061 Sunde B, Lindblad M, Malmström M et al (2021) Health-related quality of life one year after the diagnosis of oesophageal cancer: a population-based study from the Swedish National Registry for Oesophageal and Gastric Cancer. BMC Cancer 21(1):1277. 10.1186/s12885-021-09007-9 Drummond MF, Schwartz JS, Jönsson B et al (2008) Key principles for the improved conduct of health technology assessments for resource allocation decisions. Int J Technol Assess Health Care 24(3):244–258. 10.1017/S0266462308080343 Japan Council for Quality Health Care Minds Clinical Practice Guideline Development Manual 2020 ver. 3.0. https://minds.jcqhc.or.jp/methods/cpg-development/minds-manual/ last accessed;18th Feb 2024 Daroudi R, Nahvijou A, Arab M et al (2022) A cost-effectiveness modeling study of treatment interventions for stage I to III esophageal squamous cell carcinoma. Cost Eff Resource Allocation 20(1). 10.1186/s12962-022-00352-5 Gordon LG, Hirst NG, Mayne GC et al (2012) Modeling the cost-effectiveness of strategies for treating esophageal adenocarcinoma and high-grade dysplasia. J Gastrointest Surg 16(8). 10.1007/s11605-012-1911-9 Lin CY, Fang HY, Feng CL et al (2016) Cost-effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: A population-based matched case-control study. Thorac Cancer 7(3). 10.1111/1759-7714.12326 Guyot P, Ades AE, Ouwens MJ et al (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol 12(9). 10.1186/1471-2288-12-9 Nakanoko T, Morita M, Nakashima Y et al (2022) Nationwide survey of the follow-up practices for patients with esophageal carcinoma after radical treatment: historical changes and future perspectives in Japan. Esophagus 19(1). https://doi.org/10.1007/s10388-021-00869-3 Hagiwara Y, Shiroiwa T, Taira N et al (2020) Mapping EORTC QLQ-C30 and FACT-G onto EQ-5D-5L index for patients with cancer. Health Qual Life Outcomes 18(1). 10.1186/s12955-020-01611-w Inomata M, Shiroshita H, Uchida H et al (2020) Current status of endoscopic surgery in Japan: The 14th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery. Asian J Endosc Surg 13(1):7–18. 10.1111/ases.12768 Low DE, Allum W, Manzoni GD et al (2019) Guidelines for perioperative care in esophagectomy: nhanced recovery after surgery (ERAS) Society commendations. World J Surg 43(2):299–330. 10.1007/s00268-018-4786-4 Markar SR, Karthikesalingam A, Low DE (2015) Enhanced recovery pathways lead to an improvement in postoperative outcomes following esophagectomy: systematic review and pooled analysis. Dis Esophagus 28(5):468–475. 10.1111/dote.12214 Triantafyllou T, Olson MT, Theodorou D et al (2020) Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis. Esophagus 17(2):100–112. 10.1007/s10388-020-00718-9 Numasaki H, Teshima T, Okuda Y et al (2020) Japanese structure survey of radiation oncology in 2013. J Radiat Res 61(5):799–816. 10.1093/jrr/rraa047 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 01 Mar, 2026 Reviewers invited by journal 01 Mar, 2026 Editor assigned by journal 24 Feb, 2026 First submitted to journal 18 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8915993","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":598914931,"identity":"43701678-23b9-4092-9bb8-582b4406a35c","order_by":0,"name":"Takuro Ariga","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACA2YIncDP3gDiWpCgRbLnAIgrQYQWKJ1gcCMBRBOhxZydO/ED457DeQw3n1/d8KNAgoG/vTsBrxbLZt7NEgzPDhczzs4pu9kDdJjEmbMb8DvsMO82BoYDhxObpXPSbvAAtRhI5BKppU3yTNrNPyRp6ZFgP3abWFs2SyQcSE+cwZPDdlvGQIKHsF/On9344cMB68T9x48/u/nmj40cf3svfi1gkAAmecBxxENYOQKwPyBF9SgYBaNgFIwgAABLV0jxCd/SnAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-9878-0137","institution":"Nakagami Hospital","correspondingAuthor":true,"prefix":"","firstName":"Takuro","middleName":"","lastName":"Ariga","suffix":""},{"id":598914932,"identity":"2ab2d9f1-3bcd-4c69-9468-9aa5d99fccdf","order_by":1,"name":"Kensuke Moriwaki","email":"","orcid":"","institution":"Ritsumeikan University: Ritsumeikan Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Kensuke","middleName":"","lastName":"Moriwaki","suffix":""},{"id":598914933,"identity":"cef0506e-6ea1-44c8-9a89-70b08f37e547","order_by":2,"name":"Kousuke Morimoto","email":"","orcid":"","institution":"Ritsumeikan University: Ritsumeikan Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Kousuke","middleName":"","lastName":"Morimoto","suffix":""},{"id":598914934,"identity":"4ce9d6f2-a30d-45ab-a31e-467d38537517","order_by":3,"name":"Katsuyuki Sakanaka","email":"","orcid":"","institution":"Kyoto University: Kyoto Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Katsuyuki","middleName":"","lastName":"Sakanaka","suffix":""},{"id":598914935,"identity":"a818ea45-5bb1-4b0c-9e42-6721243a34ab","order_by":4,"name":"Yoshinori Ito","email":"","orcid":"","institution":"Showa Daigaku - Hatanodai Campus: Showa Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Yoshinori","middleName":"","lastName":"Ito","suffix":""},{"id":598914936,"identity":"6de0ca81-53c6-4c7d-9eec-db9c2e5d29c2","order_by":5,"name":"Tetsuo Saito","email":"","orcid":"","institution":"Saiseikai Kumamoto Byoin","correspondingAuthor":false,"prefix":"","firstName":"Tetsuo","middleName":"","lastName":"Saito","suffix":""},{"id":598914937,"identity":"b8675be6-8481-41d8-9f75-4763f57e3859","order_by":6,"name":"Atsuto Katano","email":"","orcid":"","institution":"Tokyo Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Atsuto","middleName":"","lastName":"Katano","suffix":""},{"id":598914938,"identity":"c6a075e9-1689-4d5a-9b4d-95872e241c46","order_by":7,"name":"Satoru Matsuda","email":"","orcid":"","institution":"Keio University: Keio Gijuku Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Satoru","middleName":"","lastName":"Matsuda","suffix":""},{"id":598914939,"identity":"26454555-5e9f-40d5-9e11-b74b6c91a612","order_by":8,"name":"Ken Kato","email":"","orcid":"","institution":"National Cancer Center Hospital: Kokuritsu Gan Kenkyu Center Chuo Byoin","correspondingAuthor":false,"prefix":"","firstName":"Ken","middleName":"","lastName":"Kato","suffix":""},{"id":598914940,"identity":"dea6d2cd-3aa3-4d47-9a4e-09e04ea43ed9","order_by":9,"name":"Hiroya Takeuchi","email":"","orcid":"","institution":"Hamamatsu University School of Medicine: Hamamatsu Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Hiroya","middleName":"","lastName":"Takeuchi","suffix":""},{"id":598914941,"identity":"34af8a34-d968-4e7b-9237-28cf9c6b22ee","order_by":10,"name":"Hiroshi Onishi","email":"","orcid":"","institution":"Yamanashi Daigaku - Kofu Campus: Yamanashi Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Onishi","suffix":""}],"badges":[],"createdAt":"2026-02-19 09:28:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8915993/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8915993/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104180696,"identity":"c2999023-c9af-4e35-aedc-c0b8660819a3","added_by":"auto","created_at":"2026-03-08 17:23:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56054,"visible":true,"origin":"","legend":"\u003cp\u003ePartitioned survival analysis model. For each treatment group, each node is continuously present for an arbitrary amount of time until the status changes (curved arrows) and moves to the next node when there is a status transition (straight arrows).\u003c/p\u003e\n\u003cp\u003eAbbreviations: CRT: chemoradiotherapy, PD: progressive disease, PFS: progression-free survival, ST: surgical therapy.\u003c/p\u003e","description":"","filename":"Onlinefig1.png","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/cff171800b42cae3f383c6b0.png"},{"id":104180706,"identity":"6711a513-ffb4-4972-bde9-81b2b3967997","added_by":"auto","created_at":"2026-03-08 17:23:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33952,"visible":true,"origin":"","legend":"\u003cp\u003eFitting a parametric function to the Kaplan-Meier curve. The percentage of surviving patients is shown on the vertical axis of each figure. Figure 2a shows the ST group curves. The area under the curve in blue represents the mean survival time in the patients with PD, and the area under the curve in grey represents the mean time of progression-free survival.\u003c/p\u003e\n\u003cp\u003eFigure 2b shows the CRT group curves. The area under the curve in light blue represents the mean survival time of patients with PD without an esophagus, the area under the curve in blue represents the mean survival time of patients with PD with an esophagus, and the area under the curve in grey represents the mean PF survival time.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CRT: chemoradiotherapy, PD: progressive disease, PFS: progression-free, ST: surgical therapy.\u003c/p\u003e","description":"","filename":"Onlinefig2.png","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/595895bd00d4b3c68d9de052.png"},{"id":104180744,"identity":"bbb03cac-19db-4046-b405-e064b2b30b4a","added_by":"auto","created_at":"2026-03-08 17:23:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":38083,"visible":true,"origin":"","legend":"\u003cp\u003eResults of the tornado diagram of the deterministic sensitivity analysis. The maximum and minimum values are appended to the bar chart for each parameter.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CRT: chemoradiotherapy, PD: progressive disease, PFS: progression-free, ST: surgical therapy, USD: US Dollar, QALY: quality-adjusted life years.\u003c/p\u003e","description":"","filename":"Onlinefig3.png","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/49b2aaec0af72b076304ee14.png"},{"id":104180695,"identity":"eec2864d-ba37-44c4-a945-7c48b6aa7cb1","added_by":"auto","created_at":"2026-03-08 17:23:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":71425,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analysis. Figure 4a shows a scatter plot, Figure 4b shows the cost-effectiveness acceptability curves.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CRT: chemoradiotherapy, ICER: incremental cost-effectiveness ratio, USD: US Dollar, QALY: quality-adjusted life years, ST: surgical therapy, WTP: willingness-to-pay.\u003c/p\u003e","description":"","filename":"Onlinefig4.png","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/f9c5cc682b605b66145c6bd6.png"},{"id":104180707,"identity":"ee70997f-4ddf-4fab-8358-5bac0d894558","added_by":"auto","created_at":"2026-03-08 17:23:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":46141,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity analysis for OS. Figure5 shows the change in WTP varies according to the HR for OS in the ST group. When HR was set as 1.016, the WTP exceeded $50000.\u003c/p\u003e\n\u003cp\u003eAbbreviations: ICER: incremental cost-effectiveness ratio, HR: hazard ratio, USD: US Dollar, QALY: quality-adjusted life years, ST: surgical therapy, WTP: willingness-to-pay.\u003c/p\u003e","description":"","filename":"Onlinefig5.png","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/4cf3a61d402c59240e505a32.png"},{"id":104404240,"identity":"0734c58e-d307-4ff1-8c87-e81cd7a6688d","added_by":"auto","created_at":"2026-03-11 12:19:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1396381,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8915993/v1/57be19b4-f7a4-4dfe-999e-74667212a559.pdf"}],"financialInterests":"","formattedTitle":"Cost-Effectiveness Analysis of Chemoradiotherapy Compared to Surgery in Patients with Stage I Esophageal Squamous Cell Carcinoma in Japan","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the Japanese cancer statistics published by the National Cancer Center [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], the incidence of esophageal cancer in Japan in 2019 was 20.9 cancers per 100,000 people, and the mortality was 8.9 deaths per 100,000 people. According to the data from the National Esophageal Cancer Registry of the Japanese Esophageal Cancer Association [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], the proportion of stage I (TNM 8th Edition [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]) patients is the highest incidence rate, accounting for 39.2%. The JCOG0502 study [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] by the Japan Clinical Oncology Group (JCOG) compared esophagectomy and chemoradiotherapy (CRT) for stage I esophageal squamous cell carcinoma. Results of this study showed that the overall survival (OS) rates of patients treated with CRT were non-inferior compared with surgical treatment (ST) (hazard ratio [HR] 1.052 [95% confidence interval [CI]: 0.674\u0026ndash;1.640]), however, ST obtained a longer progression-free survival (PFS) (HR: 1.478 [95% CI: 1.01\u0026ndash;2.16]). Therefore, the Japanese Guidelines for Esophageal Cancer (GL2022) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] suggest considering ST but also recommend CRT followed by appropriate monitoring and salvage therapy for patients who wish to preserve their esophagus.\u003c/p\u003e \u003cp\u003eIn addition to OS and PFS, health-related quality of life (HRQOL) must be considered when choosing treatment modalities. There have been a few published reports on HRQOL of patients with esophageal cancer who underwent ST or CRT [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Ariga et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. showed that patients undergoing CRT had significantly better HRQOL than ST, while Chen et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. concluded that ST was better HRQOL than CRT for some of the Quality-of-Life Questionnaire (QLQ)-C30 items. Sunde et al [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. concluded that the advantages of ST and CRT varied depending on survey item in QLQs. Therefore, the HRQOL evaluations of patients with early esophageal cancer receiving ST vs CRT remain uncertain.\u003c/p\u003e \u003cp\u003eFurthermore, evaluations from a health economics perspective have become increasingly important in recent years. Since the 1990s, health technology assessments (HTAs) and approaches to decision-making on healthcare policy have been adopted by various countries, which have used them to determine whether drugs and medical technologies can be reimbursed by public insurance and set prices [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In 2021, the development of Japanese medical practice guidelines [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] included a section on evaluating health economic. Health economic evaluations of the treatments for esophageal cancer have been performed by other countries [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], but there is no the cost-effectiveness of CRT compared with ST for stage I esophageal cancer based on the Japanese insurance system.\u003c/p\u003e \u003cp\u003eTherefore, we analyzed the cost-effectiveness and HRQOL of ST versus CRT for esophageal cancer, aiming to support treatment planning and guide healthcare policy.\u003c/p\u003e"},{"header":"Materials and Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eModel-based cost-effectiveness analysis\u003c/h2\u003e \u003cp\u003eA partitioned survival analysis model (PartSA) was used to assess the cost-effectiveness of CRT compared with ST. The patients who underwent ST were stratified into 3 statuses as follows: \u0026ldquo;progression-free survival (PFS) after esophagectomy\", \"survival with progressive disease (PD) after esophagectomy\", and \"death\" (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Since patients who underwent CRT could survive with the esophagus preserved, the patients were stratified into 4 statuses as follows: \"PFS with esophagus preserved\", \"PD with esophagus preserved\", \"PD after esophagectomy\", and \"death\" (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These models were used to predict long-term medical costs, duration of survival, and quality-adjusted life years (QALY) for both the ST and CRT patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eUtility weights and cost per cycle were parameterized for each stratified patient statuses. For this analysis, parametric survival values were fitted to the Kaplan-Meier survival curves of patients in the JCOG0502 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] that were based on esophagectomy-free survival (EFS), PFS, and OS. The parameters on the EFS, PFS, and OS Kaplan-Meyer graphs were then used to calculate changes over time in the proportions of surviving patients. The proportions and expected costs and QALYs for each stratified statuses were calculated to obtain the incremental cost-effectiveness ratio (ICER) of CRT compared to ST. ICER was expressed as \"incremental cost divided by QALY\", and this represents the additional cost required for the CRT patients to gain 1 QALY greater than the ST patients.\u003c/p\u003e \u003cp\u003eAlthough there is no explicit threshold for ICER regarding cancer treatments in Japan, the Central Social Insurance Medical Council's cost-effectiveness evaluation system operate if estimated ICERs for treating a fatal disease such as cancer range from \u003cspan\u003e$\u003c/span\u003e50,000 to \u003cspan\u003e$\u003c/span\u003e75,000/QALY (at \u003cspan\u003e$\u003c/span\u003e1\u0026thinsp;=\u0026thinsp;150 yen, 7.5 to 11.25\u0026nbsp;million yen/QALY), from \u003cspan\u003e$\u003c/span\u003e75,000 to \u003cspan\u003e$\u003c/span\u003e100,000/QALY (11.25 to 15\u0026nbsp;million yen/QALY), and greater than \u003cspan\u003e$\u003c/span\u003e100,000/QALY (15\u0026nbsp;million yen/QALY ), the adjusted portion of the official price is adjusted downward by 30%, 60% and 90% respectively. For this reason, these price adjustment thresholds were also used in this study as reference values for socially acceptable values of ICER.\u003c/p\u003e \u003cp\u003e The period of analysis (time horizon) was set at 40 years, and the discount rate of 2% per year was applied to the long-term costs and benefits, as based on the national cost-effectiveness evaluation guidelines. The cycle length of the model was set at one month. TreeAge Pro Healthcare 2022 was used to construct and simulate the model. Ethical review was not applicable because all data used for the model and analysis were obtained from existing databases or published papers.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParameter settings\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSurvival curves\u003c/h2\u003e \u003cp\u003eThe PartSA model was used to extrapolate the EFS, PFS, and OS for each treatment group. Recently, Guyot et al [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. proposed a method to construct data on patient survival times data from images of Kaplan-Meier curves and number at-risk information by simulation. The procedure they used was as follows: data from graphs showing time vs. probability of cumulative survival times were extracted from images of Kaplan-Meier curves. Then, based on the plot data and the number at risk reported in the clinical trials, they created patient datasets.\u003c/p\u003e \u003cp\u003eIn this study, we used the Kaplan-Meier EFS, PFS, and OS curves from the JCOG0502 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and fit several parametric functions to create patient datasets. We used WebPlotDigitizer (Version 4.6) to extract plot information. R (version 4.2.0) and R studio (2022.02.2 Build 485) were also used to create patient datasets. To select the optimal function, we referred to the good visual fit to the Kaplan-Meier curves of the JCOG0502 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and the metrics provided by the Akaike Information Criterion and Bayesian Information Criterion, which express the degree of fit. As a result, the Weibull function was judged to be the best fit, and we used this function to perform calculations in the basic analysis. We estimated outcomes by extrapolating the OS of CRT group to that of the ST group, assuming similar OS rates for both groups. When PFS and EFS intersected with OS in the long-term extrapolation, we estimated outcomes by substituting OS values for PFS and EFS in subsequent years.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCosts\u003c/h3\u003e\n\u003cp\u003eIn this model, only direct medical costs were considered from the perspective of Japanese public medical payers, and the following cost parameters were established: i) treatment cost of ST group (/patient), ii) medical cost for PFS after esophagectomy in the ST group (/month), iii) medical cost for PD after esophagectomy in the ST group (/month), iv) treatment cost of CRT group (/patient), v) medical cost for PFS with esophagus preserved in the CRT group (/month), vi) medical cost for PD with esophagus preserved in the CRT group (/month), vii) medical cost for PD after esophagectomy in the CRT group (/month), and viii) terminal care cost in both group (/patient) (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eCalculations of the above cost parameters were based on the Diagnosis Procedure Combination/Per-Diem Payment System (DPC/PDPS), a Japanese public insurance reimbursement system, and the claims database provided by the Japan Medical Data Center (JMDC) (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe DPC/PDPS consists of two parts: the comprehensive portion, which pays a fixed fee per diem based on the diagnosis; and the piecework portion, which pays based on the treatments that were performed. The comprehensive component was defined as 33 days for the ST group and 14 days for the CRT group, in accordance with the mean duration of hospitalization as reported in the DPC/PDPS 2024.\u003c/p\u003e \u003cp\u003eFor the ST group, a continuous hospitalization period was implemented. The surgical fee model was based on an open esophagectomy with three-field lymph node dissection, gastric tube reconstruction, and anesthesia fees. For the CRT group, the radiation fee model was based on the four-field irradiation technique, and 2 cycle chemotherapy comprised seven consecutive days of hospitalization. Outpatient irradiation fees were incorporated into the piecework portion during outpatient visits.\u003c/p\u003e \u003cp\u003eThe JMDC claims database is Japan's largest privately available epidemiological claims database. It accumulates subscriber registers, receipts (inpatient, outpatient, and prescription), and data from health checkups provided by insurers. The database assigns a unique ID to each subscriber, which allows the tracing of transfers and visits to multiple facilities. However, elderly patients older than 75 years are not included in the JMDC database because of variations in the different insurance medical fee systems in Japan.\u003c/p\u003e \u003cp\u003eIn this study, during the period from January 2005 to March 2021, we selected for analysis case histories with the standard diagnostic categories that related to esophageal cancer (N\u0026thinsp;=\u0026thinsp;62,247). The extracted data was processed into a panel format of data over time to simplify the tabulation of changes in medical costs over time.\u003c/p\u003e \u003cp\u003eThe initial treatment costs in cost parameters i) and iv) were based on the DPC/PDPS 2024. For the follow-up examinations in cost parameters ii) and v), we built models based on the post-treatment survey date by Nakanoko et al [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and calculated based on the DPC/PDPS 2024.\u003c/p\u003e \u003cp\u003eThe pre-death medical expenditures of patients with esophageal cancer showed that the consumption of medical resources increased two months before death, peaked in the month before death, and decreased in the month after death. We defined the total medical cost in the three months before death as cost parameter viii).\u003c/p\u003e \u003cp\u003eThe JMDC claims database does not explicit the recurrence of cancer. We performed an exploratory simulation of the PartSA model in the base case setting and found that the duration of PD in CRT group was about 23\u0026thinsp;~\u0026thinsp;24 months. Therefore, we assumed that the two years before the terminal stage (4\u0026thinsp;~\u0026thinsp;28 months before death) was the period with PD and estimated the cost parameters iii), vi), and vii). In this analysis, the ST and CRT groups were assumed to have the same medical costs for PD and end-of-life care.\u003c/p\u003e\n\u003ch3\u003eUtility weights\u003c/h3\u003e\n\u003cp\u003eThe utility weights for each status were estimated based on published data by Ariga et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The mapping algorithm used from EORTC-QLQ30 to EQ-5D-5L that was developed by Hagiwara et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] was used to transform from EORTC-QLQ30 data to utility weights.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eIn this study, a one-way sensitivity analysis was conducted for the parameter settings in the model, and the results of this sensitivity analysis are summarized in a tornado diagram.\u003c/p\u003e \u003cp\u003eTo estimate the distribution of probabilities for ICERs and to perform a probabilistic assessment of cost-effectiveness, we performed a probabilistic sensitivity analysis that was based on 1,000 second-order Monte Carlo simulations. We set up probability distributions limited to those parameters of the model for which information on probability distributions as 95% CI. We repeated the calculations of expected cost, expected QALY, and ICER 1,000 times by sampling the input values for each parameter from the established probability distribution. Based on results of second-order Monte-Carlo simulations, we constructed cost-effectiveness acceptability curves. We estimated the proportion of iterations in which CRT would be preferred in terms of cost-effectiveness, assuming willingness-to-pay thresholds of \u003cspan\u003e$\u003c/span\u003e50,000, \u003cspan\u003e$\u003c/span\u003e75,000, and \u003cspan\u003e$\u003c/span\u003e100,000/QALY.\u003c/p\u003e \u003cp\u003eAdditionally, as mentioned earlier, we extrapolated the OS for CRT OS to the ST group to analyze the base case. To account for the impact of OS differences, we analyzed the ICER when the OS for ST group was adjusted by plus-minus10%, with the OS for CRT group set as HR\u0026thinsp;=\u0026thinsp;1.\u003c/p\u003e \u003c/div\u003e\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"873\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Parameter settings\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eEstimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eSE/\u003c/p\u003e\n \u003cp\u003eVariability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 147px;\"\u003e\n \u003cp\u003ePlausible range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eDistribution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003eCost parameter (USD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp;ST group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Cost of esophagectomy including hospitalization (/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e20,322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e18,289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e22,354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eEO \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Medical cost in PFS state after esophagectomy (/month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eEO \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1st year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2nd year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;3rd year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;4th year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;5th year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Subsequent year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Medical cost in PD after esophagectomy (/month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1,973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eJMDC \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Terminal care cost (/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e12,175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e11,539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e12,812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eJMDC \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp;CRT group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Cost of CRT including hospitalization (/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e7,348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e6,613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e8,083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eEO \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Medical cost in PFS with esophagus preserved (/month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eEO \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1st year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2nd year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;3rd year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;4th year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;5th year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Subsequent year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Medical cost in PD with esophagus preserved (/month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1,973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eJMDC \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Cost of esophagectomy including hospitalization (/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e20,322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026plusmn;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e18,289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e22,354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eTriangle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eEO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Medical cost in PD after esophagectomy (/month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1,973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2,093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eJMDC \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; Terminal care cost (/patient)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e12,175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e11,539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e12,812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eJMDC \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003eUtility parameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; ST group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PFS after esophagectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PD after esophagectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.706\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; CRT group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PFS with esophagus preserved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.902\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PD with esophagus preserved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.827\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.765\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PD after esophagectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003eDiscount rate for cost and QALY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 417px;\"\u003e\n \u003cp\u003eTime horizon (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCRT: chemoradiotherapy, EO: expert opinion, JMDC: JMDC claims database, PD: progressive disease, PF: progression-free survival, QALY: quality-adjusted life years, ST: surgical treatment\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eBase case analysis\u003c/h2\u003e \u003cp\u003eThe Utility weight for each status was shown in Table\u0026nbsp;1, and the results of cohort simulation on trends in health status and long-term medical costs for each group are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The incremental QALY for the CRT group relative to the ST group was estimated to be 0.630. Although the initial treatment cost was lower in the CRT group, showed that the incremental total medical cost for CRT was \u003cspan\u003e$\u003c/span\u003e26,313 higher than for ST, with the ICER estimated to be \u003cspan\u003e$\u003c/span\u003e41,742/QALY.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBase case results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental\u003c/p\u003e \u003cp\u003e (vs ST)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of PFS after esophagectomy (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.969\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-14.969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of PFS with esophagus preserved (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of PD after esophagectomy (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of PD with esophagus preserved (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.487\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQALY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cost (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial treatment cost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20,163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-12,901\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical cost during PFS after esophagectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10,988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-10,988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical cost during PFS with esophagus preserved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16,538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16,538\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical cost during PD after esophagectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8,010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9,669\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost of esophagectomy in CRT group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical cost during PD with esophagus preserved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30,939\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30,939\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICER (USD/QALY gained)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41,742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCRT: chemoradiotherapy, ICER: incremental cost-effectiveness ratio, PD: progressive disease, PFS: progression-free survival, QALY: quality-adjusted life years, ST: surgical treatment\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eThe results of the deterministic sensitivity analysis are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The parameter that had a relatively large impact on the ICER in CRT was the utility weight of PD with esophagus preserved, and the variation to these parameters was in the range of \u003cspan\u003e$\u003c/span\u003e37,113/QALY to \u003cspan\u003e$\u003c/span\u003e47,690/QALY. The results suggested that ST might dominate CRT, depending on the established utility weights in PFS for the CRT and ST groups, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSensitivity analysis of utility weights\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility weight for PFS with esophagus preserved in CRT group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental cost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALY\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental QALY\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eICER\u003c/p\u003e \u003cp\u003e(USD/QALY)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDominated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.865\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90,028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41,742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.933\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.541\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27,169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20,139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility weight for PFS in ST group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCost (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental cost (USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental QALY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eICER\u003c/p\u003e \u003cp\u003e(USD/QALY)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18,773\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25,898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41,742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e107,516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74,486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDominated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCRT: chemoradiotherapy, PFS: progression-free survival, ICER: incremental cost-effectiveness ratio, QALY: quality-adjusted life years, ST: surgical treatment\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results of probabilistic sensitivity analysis are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The cost-effectiveness acceptability curve showed that CRT was more cost-effective than ST were estimated to be 59.3%, 67.5%, and 75.8%, when the acceptable values for ICER were \u003cspan\u003e$\u003c/span\u003e50,000, \u003cspan\u003e$\u003c/span\u003e75,000, and \u003cspan\u003e$\u003c/span\u003e100,000/QALY, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe result of sensitivity analysis for OS was summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003e. It showed that OS for ST group exceeded the lower bound of our ICER when the HR was set as 1.016.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR for OS in ST\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental cost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALY\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental QALY\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eICER\u003c/p\u003e \u003cp\u003e(USD/QALY)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46,190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74,489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28,299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e24,094\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47,156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74,489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27,333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e30,470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48,174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74,489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26,315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e41,744\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49,245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.829\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74,489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25,244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e67,502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50,368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74,489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24,121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e189,508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCRT: chemoradiotherapy, HR: Hazard ratio, ICER: incremental cost-effectiveness ratio, OS: Overall survival, QALY: quality-adjusted life years, ST: surgical treatment\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we compared CRT to ST for stage I esophageal cancer from the perspective of the Japanese public healthcare payer. We estimated that the incremental cost was \u003cspan\u003e$\u003c/span\u003e26,313, the incremental QALY was 0.630, and ICER was \u003cspan\u003e$\u003c/span\u003e41,742/QALY.\u003c/p\u003e \u003cp\u003eIn Japan, a system was initiated in 2019 to utilize the evidence of cost-effectiveness in the price adjustments of new medical technologies. Under this system, a rule was adopted to adjust the proportion of the calculated price of new medical technologies that corresponded to the additional premium, according to the level of ICER. For the price adjustment of items that required special consideration, three ICER thresholds were established before mentioned. Although technologies other than drugs and medical devices are currently not covered by this system, the minimum acceptable value for ICER is \u003cspan\u003e$\u003c/span\u003e50,0000/QALY, the point estimate-based result of \u003cspan\u003e$\u003c/span\u003e41,742/QALY obtained in this study showed that CRT was superior to ST in terms of cost-effectiveness. Although our sensitivity analysis indicates the superiority of CRT, the results are not robust due to several factors. First, regarding the difference in QALYs between the two groups, several articles [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] indicated that patients in the ST group may obtain improved QALYs because of less invasive treatments and the introduce of perioperative adjuvant therapy. Inomata et al [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. reported that several studies of minimally invasive esophagectomy indicated that early interventions such as perioperative rehabilitation within the Enhanced Recovery After Surgery framework can reduce various adverse events associated with ST [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These findings suggest that the comparable significance of the improved QALYs between CRT and ST is not fixed. Additionally, it should be noted that Intensity-Modulated Radiation Therapy (IMRT) is being incorporated into the CRT and is anticipated to enhance QOL by reducing the adverse events. In both groups, the treatment procedures are becoming less invasive, which is likely to affect future estimates on incremental QALYs and ICERs. From a cost perspective, the introduction of IMRT may increase the initial treatment costs for the CRT group [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and potentially alter the ICER.\u003c/p\u003e \u003cp\u003eWe employed a utility analysis developed by Ariga et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. that was conducted for ethnic groups, treatment techniques, and public insurance similar to those in the JCOG0502 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, results of utility analysis of esophageal cancer treatments vary as mentioned [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and these results are inconsistent; therefore, the construction of a model derived from multiple studies has the potential to yield divergent results. In addition, we assumed equivalent OS between the ST and CRT. However, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003e, when the OS for ST group was set at HR\u0026thinsp;=\u0026thinsp;1.016, it exceeded the lower bound of the ICER we defined. If the OS for ST group is slightly better than that for CRT, the ST could potentially be considered more cost-effective.\u003c/p\u003e \u003cp\u003eAlthough this study showed that CRT was superior in cost-effectiveness in this study, ST might be superior in cost-effectiveness influenced by various factors as mentioned above. This indicates that both ST and CRT are equally effective and cost-effective in the Japanese domestic insurance system. Therefore, treatment decisions can be made based on shared decision-making with the patient.\u003c/p\u003e \u003cp\u003eThe novelty of this study was that it used the JMDC claims database to evaluate the cost-effectiveness of CRT and ST for esophageal cancer. The JMDC claims database is the largest commercial epidemiological receipt database in Japan. Using this database, we were able to estimate ICERs that considered the real-world setting in Japan. It is also significant that we applied the EQ-5D-5L mapping algorithm to the EORTC-QLQ30 data to estimate utility weights that reflected the preferences of the general population in Japan for various health conditions of esophageal cancer patients. Our approaches could be applied to health economic evaluations of patients with other types of cancer.\u003c/p\u003e \u003cp\u003eThis study has several limitations. At first, the JMDC data only included receipt data and did not provide clinical information on patients, such as stage. Therefore, the analysis could not be limited to stage I patients. The cost of maintenance chemotherapy following CRT for stage II\u0026ndash;III patients may be perceived as an additional factor to consider. Second, clinical events such as progression depended on analytical definitions in this study. The analysis utilized surrogate triggers, such as re-initiation of surgery, radiation therapy after surgery, or chemotherapy occurring after completion of the initial therapy. Third, endoscopic treatments and photodynamic therapy could not be included as triggers because of the lack of explicit data. Fourth, the survival probabilities were based on the best visual fit and did not incorporate individual patient data from JCOG0502 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, the accuracy of specific survival probabilities may be lower than if individual patient data were used. Fifth, the insurance medical fee in Japan revises every two years, creating uncertainty on cost parameters.\u003c/p\u003e \u003cp\u003eIn conclusion, CRT for stage I esophageal cancer in Japan is likely to be more cost-effective than ST. Although further investigation of resource consumption, HRQOL, and clinical benefits in Japanese patients is needed, our approach is expected to support clinical and policy decision making.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echemoradiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprogressive disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprogression-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esurgical therapy.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclarations\u003c/h2\u003e \u003cp\u003e \u003cb\u003eof generative AI and AI-assisted technologies in the manuscript preparation process\u003c/b\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis study was supported by a specific grant from the Japanese Society for Radiation Oncology\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003e This manuscript was provided financial support by Japanese Society for Radiation Oncology.\u003c/p\u003e \u003cp\u003eThe authors are grateful to Prof. Ariga of Iwate Medical University for providing his data set.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHori M, Matsuda T, Shibata A et al (2015) Cancer incidence and incidence rates in Japan in 2009: A study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 45(9):884\u0026ndash;891. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jjco/hyv088\u003c/span\u003e\u003cspan address=\"10.1093/jjco/hyv088\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatanoda K, Hori M, Saito E et al (2021) Updated trends in cancer in Japan: Incidence in 1985\u0026ndash;2015 and mortality in 1958\u0026ndash;2018\u0026mdash;a sign of decrease in cancer incidence. J Epidemiol 31(7):426\u0026ndash;450. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2188/jea.JE20200416\u003c/span\u003e\u003cspan address=\"10.2188/jea.JE20200416\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe M, Toh Y, Ishihara R et al (2023) Comprehensive registry of esophageal cancer in Japan, 2015. Esophagus 20(1):1\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10388-022-00950-5\u003c/span\u003e\u003cspan address=\"10.1007/s10388-022-00950-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrierley JD, Gospodarowicz MK (2017) Christian Wittekind. TNM Classification of Malignant Tumours, 8th Edition. New York: Wiley-Blackwell\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKato K, Ito Y, Nozaki I et al (2021) Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma. Gastroenterology 161(6):1878\u0026ndash;1886e2. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.gastro.2021.08.007\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2021.08.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitagawa Y, Ishihara R, Ishikawa H et al (2023) Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus 20(3):343\u0026ndash;372. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10388-023-00993-2\u003c/span\u003e\u003cspan address=\"10.1007/s10388-023-00993-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitagawa Y, Ishihara R, Ishikawa H et al (2023) Esophageal cancer practice guidelines 2022 edited by the Japan Esophageal Society: part 2. Esophagus 20(3):373\u0026ndash;389. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10388-023-00994-1\u003c/span\u003e\u003cspan address=\"10.1007/s10388-023-00994-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAriga H, Nemoto K, Miyazaki S et al (2009) Prospective Comparison of Surgery Alone and Chemoradiotherapy With Selective Surgery in Resectable Squamous Cell Carcinoma of the Esophagus. Int J Radiat Oncol Biol Phys 75(2):348\u0026ndash;356. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijrobp.2009.02.086\u003c/span\u003e\u003cspan address=\"10.1016/j.ijrobp.2009.02.086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen CY, Hsieh VCR, Chang CH et al (2017) Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients. Dis Esophagus 30(10):1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/dote/dox061\u003c/span\u003e\u003cspan address=\"10.1093/dote/dox061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSunde B, Lindblad M, Malmstr\u0026ouml;m M et al (2021) Health-related quality of life one year after the diagnosis of oesophageal cancer: a population-based study from the Swedish National Registry for Oesophageal and Gastric Cancer. BMC Cancer 21(1):1277. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12885-021-09007-9\u003c/span\u003e\u003cspan address=\"10.1186/s12885-021-09007-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrummond MF, Schwartz JS, J\u0026ouml;nsson B et al (2008) Key principles for the improved conduct of health technology assessments for resource allocation decisions. Int J Technol Assess Health Care 24(3):244\u0026ndash;258. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/S0266462308080343\u003c/span\u003e\u003cspan address=\"10.1017/S0266462308080343\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJapan Council for Quality Health Care Minds Clinical Practice Guideline Development Manual 2020 ver. 3.0. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://minds.jcqhc.or.jp/methods/cpg-development/minds-manual/\u003c/span\u003e\u003cspan address=\"https://minds.jcqhc.or.jp/methods/cpg-development/minds-manual/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e last accessed;18th Feb 2024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaroudi R, Nahvijou A, Arab M et al (2022) A cost-effectiveness modeling study of treatment interventions for stage I to III esophageal squamous cell carcinoma. Cost Eff Resource Allocation 20(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12962-022-00352-5\u003c/span\u003e\u003cspan address=\"10.1186/s12962-022-00352-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGordon LG, Hirst NG, Mayne GC et al (2012) Modeling the cost-effectiveness of strategies for treating esophageal adenocarcinoma and high-grade dysplasia. J Gastrointest Surg 16(8). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11605-012-1911-9\u003c/span\u003e\u003cspan address=\"10.1007/s11605-012-1911-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin CY, Fang HY, Feng CL et al (2016) Cost-effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: A population-based matched case-control study. Thorac Cancer 7(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/1759-7714.12326\u003c/span\u003e\u003cspan address=\"10.1111/1759-7714.12326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuyot P, Ades AE, Ouwens MJ et al (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol 12(9). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1471-2288-12-9\u003c/span\u003e\u003cspan address=\"10.1186/1471-2288-12-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakanoko T, Morita M, Nakashima Y et al (2022) Nationwide survey of the follow-up practices for patients with esophageal carcinoma after radical treatment: historical changes and future perspectives in Japan. Esophagus 19(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10388-021-00869-3\u003c/span\u003e\u003cspan address=\"10.1007/s10388-021-00869-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHagiwara Y, Shiroiwa T, Taira N et al (2020) Mapping EORTC QLQ-C30 and FACT-G onto EQ-5D-5L index for patients with cancer. Health Qual Life Outcomes 18(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12955-020-01611-w\u003c/span\u003e\u003cspan address=\"10.1186/s12955-020-01611-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInomata M, Shiroshita H, Uchida H et al (2020) Current status of endoscopic surgery in Japan: The 14th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery. Asian J Endosc Surg 13(1):7\u0026ndash;18. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ases.12768\u003c/span\u003e\u003cspan address=\"10.1111/ases.12768\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLow DE, Allum W, Manzoni GD et al (2019) Guidelines for perioperative care in esophagectomy: nhanced recovery after surgery (ERAS) Society commendations. World J Surg 43(2):299\u0026ndash;330. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00268-018-4786-4\u003c/span\u003e\u003cspan address=\"10.1007/s00268-018-4786-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkar SR, Karthikesalingam A, Low DE (2015) Enhanced recovery pathways lead to an improvement in postoperative outcomes following esophagectomy: systematic review and pooled analysis. Dis Esophagus 28(5):468\u0026ndash;475. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/dote.12214\u003c/span\u003e\u003cspan address=\"10.1111/dote.12214\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTriantafyllou T, Olson MT, Theodorou D et al (2020) Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis. Esophagus 17(2):100\u0026ndash;112. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10388-020-00718-9\u003c/span\u003e\u003cspan address=\"10.1007/s10388-020-00718-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNumasaki H, Teshima T, Okuda Y et al (2020) Japanese structure survey of radiation oncology in 2013. J Radiat Res 61(5):799\u0026ndash;816. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jrr/rraa047\u003c/span\u003e\u003cspan address=\"10.1093/jrr/rraa047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Esophageal cancer, Cost-effective analysis, QOL, ICER, chemoradiotherapy.","lastPublishedDoi":"10.21203/rs.3.rs-8915993/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8915993/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eWe performed a model-based cost-effectiveness analysis of the use of surgical treatment (ST) versus chemoradiotherapy (CRT) for stage I esophageal cancer in Japan.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eA model for partitioned survival analysis was developed to estimate the long-term medical costs and quality-adjusted life years (QALYs) for patients who had received either ST or CRT. Data on survival times were taken from the JCOG0502 trial. Utility values were estimated by applying a mapping algorithm based on Japanese data from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire. From the perspective of public healthcare, only direct medical costs were considered. A discount rate of 2% per year was applied to long-term costs and QALYs to estimate the incremental cost-effectiveness ratio (ICER) of CRT compared to ST.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe incremental cost of CRT versus ST was estimated to be \u003cspan\u003e$\u003c/span\u003e26,313 (USD), the incremental QALY was 0.630, and the ICER was \u003cspan\u003e$\u003c/span\u003e41,742/QALY. Sensitivity analysis showed that the parameter with a relatively large effect on the ICER was the utility weight of progressive disease with esophagus preserved patients in CRT. The variations in ICERs ranged from approximately \u003cspan\u003e$\u003c/span\u003e37,113/QALY to \u003cspan\u003e$\u003c/span\u003e47,690/QALY. With willingness-to-pay thresholds ranging from \u003cspan\u003e$\u003c/span\u003e50,000/QALY to \u003cspan\u003e$\u003c/span\u003e100,000/QALY, CRT was more cost-effective than ST, with the probability of being cost-effective estimated to range from 59.3% to 76.3%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn Japan, CRT for stage I esophageal cancer may be more cost-effective than ST, if the acceptable ICER is \u003cspan\u003e$\u003c/span\u003e50,000/QALY.\u003c/p\u003e","manuscriptTitle":"Cost-Effectiveness Analysis of Chemoradiotherapy Compared to Surgery in Patients with Stage I Esophageal Squamous Cell Carcinoma in Japan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 17:23:06","doi":"10.21203/rs.3.rs-8915993/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-03-02T00:03:11+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-01T22:58:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-24T08:44:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2026-02-19T04:27:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ce752405-0107-40e0-b0f6-01e718fbc1b8","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-08T17:23:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 17:23:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8915993","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8915993","identity":"rs-8915993","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}