Cost-effectiveness Analysis of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer

Cost-effectiveness Analysis of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer | 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 Article Cost-effectiveness Analysis of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer Hui Zhang, Yuhang Liu, Guihao Zeng, Shuangshuang Hu, Haonan Li, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6470075/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background Moderately Hypofractionated Radiation Therapy (Hypo-RT) has been considered as an alternative strategy for unresectable stage III non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy, with potential benefits in overall survival and local control. In this study, we compared the cost-effectiveness of Hypo-RT with that of Con-RT in patients with unresectable stage III non-small cell lung cancer receiving concurrent chemotherapy. Objectives Both prospective and retrospective studies have demonstrated that, compared with Con-RT, Hypo-RT resulted in superior local control of the primary disease without an increase in major toxicity in patients with medically inoperable stage III NSCLC. However, to the best of our knowledge, the economic value of using this new therapy for this indication is currently unknown. Therefore, our study aimed to evaluate the cost-effectiveness of Hypo-RT for the standard-of-care treatment of medically inoperable, early-stage NSCLC. Methods A three-stage Markov model over a 5-year lifetime horizon was developed to compare the cost and effectiveness of Hypo-RT with that of Con-RT. The primary outcomes of our study included life years (LYs) total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. Results In the base case analysis, the cost and QALYs of Hypo-RT were $ 123,721.28 and 2.23, while for Con-RT, the cost and QALYs were $ 187,803.55 and 1.69, respectively. Hypo-RT is a more cost-effective strategy compared with Con-RT for medically inoperable stage III NSCLC, with $ 118,848.20 is saved for every incremental QALY. This result was validated by DSA and PSA, in which SBRT remained the most cost-effective option. Hypo-RT was dominant compared to Con-RT, and Hypo-RT was the most cost-effective option. Conclusions Hypo-RT is likely to be a cost-effective option compared with Con-RT for patients with unresectable stage III non-small cell lung cancer receiving concurrent chemotherapy. Biological sciences/Drug discovery/Pharmacology/Clinical pharmacology Biological sciences/Drug discovery/Pharmacology/Pharmacodynamics non-small cell lung cancer cost-effectiveness analysis hypofractionated radiation therapy conventional radiation therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1 Introduction In 2022, lung cancer accounted for approximately 2.5 million new diagnoses and 1.8 million deaths globally, representing the most prevalent cause of cancer-related morbidity and mortality. Non-small cell lung cancer (NSCLC) constituted 12.4% of all new cancer cases (1 in 8) and 18.7% of cancer deaths (1 in 5), imposing substantial physical, psychological, and socioeconomic burdens on affected individuals, their communities, and healthcare infrastructures worldwide ( 1 – 3 ). The emergence of numerous novel medicines improves the survival outcomes of NSCLC. Nevertheless, the price of new medicines for individuals, which also significantly strains healthcare systems, especially in Northern America, Eastern Asia, and Northern Europe ( 1 ). Stage III NSCLC, also called locally advanced NSCLC, accounts for 30% of NSCLC patients ( 4 ). Many of them have smoking-related cardiac or respiratory comorbidities that make them unfit for an operation. Historically, concurrent/sequential chemotherapy and radiation therapy (RT) with conventional fractionation of 60 Gy administered in 30 fractions was the standard treatment for patients with unresectable stage III NSCLC ( 5 ). Although treatment paradigms for stage III NSCLC have evolved significantly from radiotherapy alone in the 1980s to contemporary concurrent chemoradiotherapy regimens, long-term outcomes remain unsatisfactory, with 5-year survival rates plateauing at 15–20% ( 6 ). Despite the availability of curative-intent treatment strategies, surgery remains the standard-of-care for resectable, early-stage and functionally operable NSCLC ( 7 – 9 ). Nevertheless, numerous patients suffer from smoking-related cardiac or respiratory comorbidities that render them unsuitable candidates for surgery. For such individuals, radiotherapy emerges as a safer and potentially curative alternative ( 6 ). Historically, patients with inoperable early-stage NSCLC were treated with conventional radiation therapy (Con-RT). Based on Con-RT, Hypofractionated-RT (Hypo-RT) has been developed in recent years. Hypo-RT is characterized by a high local dose of radiation given in fewer fractions as an ablative treatment, usually 60–80 Gy in 3.0–4.0 Gy fractions ( 10 ). Both prospective and retrospective studies have demonstrated that, compared with Con-RT, Hypo-RT resulted in superior local control of the primary disease without an increase in major toxicity in patients with medically inoperable stage I NSCLC ( 11 ). Therefore, Hypo-RT has emerged as a new technology in the treatment of NSCLC and has been gradually incorporated into clinical practice in China ( 12 ). Given the escalating prevalence of NSCLC and progressive cost burden associated with disease management, rigorous cost-effectiveness evaluations of novel therapies are imperative ( 13 , 14 ). This analysis is based on data from the multicenter randomized phase 3 trial, which compared Hypo-RT (60 Gy/20 fractions) with Con-RT (60 Gy/30 fractions) in unresectable stage III NSCLC patients receiving concurrent chemotherapy. To our knowledge, this represents the first cost-effectiveness study of Hypo-RT in the Chinese context. Using a Markov decision-analytic model, we evaluate the economic value of Hypo-RT versus Con-RT, aiming to inform clinical practice and healthcare reimbursement policies. 2 Materials and methods 2.1 Patients and intervention The enrolled patients were all derived from the randomized, multicentre, nonblinded phase 3 clinical trial. NSCLC patients with unresectable stage III non-small cell lung cancer were recruited. Patients were randomized at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). A total of 146 patients were enrolled and randomized at a 1:1 ratio: 73 to the Hypo-RT group (60 Gy in 20 fractions) and 73 to the Con-RT group (60 Gy in 30 fractions). Among these, 42 patients in the Hypo-RT group also received amivantamab-lazertinib. Hypo-RT was delivered at 3 Gy per fraction, while Con-RT was administered at 2 Gy per fraction, both on a Monday-to-Friday schedule. RT was delivered by Tomotherapy using a 6 MV beam in the Hypo-RT group and by IMRT (6–18 MV) in the Con-RT group. All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy ( 11 ). All research methods were strictly conducted in accordance with relevant guidelines and regulations. This study was based on data from a multicenter randomized phase III clinical trial, which was approved by the Ethics Committee of Zhongshan Hospital (Approval No.: 2018ZSLC26). Written informed consent was obtained from all participants or their legal guardians before participation in the study. In our study, we assumed that the patients with a baseline weight of 70 kg, body surface area of 1.86 m 2 , and a creatinine clearance of 70 mL/min as standard ( 15 ). Only when the grade of adverse events (AEs) ≥ grade 3 (G3) in either the Hypo-RT or Con-RT group, AEs were identified for analysis. This study was carried out based on the phase 3 trial and did not involve other human participants. Hence, there is no need for the approval of the independent ethics committee. 2.2 Model construction A three-stage Markov model was established by the Microsoft Excel 2023 software, including PFS, progressive disease (PD), and death (Fig. 1). We extended the simulation period to 5 years, the simulated PFS and overall survival (OS) fitted with different distributions were displayed in Fig. 2 . The simulation cycle duration was 3 weeks. In this study, a 3% annual discount rate was applied for future health utility and cost ( 16 ). The analysis included three key parameters: life years (LYs) total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs from previous years were adjusted using the consumer price index for healthcare of 2016–2023 and were shown in 2023 US dollars (1 USD = 7.08 CNY). A willingness-to-pay (WTP) threshold was set as the forecasted gross domestic product (GDP) per capita at $ 12,621.19 (￥89,358)- $ 37,863.51(￥268,074), which was taken from the Statistical Communiqué of the People’s Republic of China on the 2023 National Economic and Social Development. A treatment was considered cost-effective if its calculated ICER was lower than this established threshold ( 17 ). Table 1 Cost-effectiveness analytical framework Category Intervention Comparator Hypo-RT Con-RT Population Patients with unresectable stage III non-small cell lung cancer Decision-analytical model Markov model Outcomes Direct medical costs, quality-adjusted life-year, and incremental cost-effectiveness ratio Disease model Progression-free state, progressed-disease state, and death Cycle length 3 weeks Time horizon 5 years Discount rate 3% Willingness-to-pay Forecasted gross domestic product per capita in 2023 Measurements ICER, incremental cost-effectiveness ratio Scenario analysis Gradual 10% price reduction of hypo-RT, using life-years to measure effectiveness, using second-best fit survival models, applying a conversion factor to nonmedication costs, and assuming adverse events incurred every cycle during the first six months and the entire time horizon. 2.3 Model survival and transition probabilities The OS and PFS data of Hypo-RT and Con-RT were extracted by the GetData Graph Digitizer. The estimates of the OS curve and PFS curve for all groups were reconstructed by R software. A series of statistical distributions, such as the Log-logistic, Log-normal, Weibull, Gompertz, Exponential, and Gamma distributions were utilized to fit the pseudo-individual patient data set. This study chose the most suitable survival function with the lowest Akaike information criterion (AIC) and Bayesian information criterion values (BIC) ( 18 ). Detailed model diagnostics were presented in Tables 1 and 2 . The shape parameter (λ) and the scale parameter (γ) of the suitable function were gained from R software. 2.4 Cost and utility estimates From the perspective of the healthcare system, our research only focused on the direct medical costs, including the cost of radiotherapy, the cost of chemotherapy, the drug costs, the costs of adverse effect managements, the cost of monthly best supportive care, the cost of abdomen enhanced CT, the cost of chest enhanced CT and the cost of MRI. AEs were considered to include grade ≥ 3 adverse events: acute radiation pneumonitis (RP), leukopenia, anemia, late RP, late RE, and platelet count decreased. related treatment costs were derived from the published literature, and on this basis, opinions of clinical experts were considered (including 23 clinical experts from more than 11 grade A tertiary hospitals in 3 provinces in China). Monitoring frequencies of unresectable stage III NSCLC were driven from drug package inserts and the CSCO Guidelines for NSCLC (2023) ( 30 ). QALYs were used to assess the effectiveness of each health condition. The utilities of PFS and PD in our model were 0.81 and 0.67 ( 18 ). To evaluate the negative effect of AEs, the disutility of AEs was also considered in this model ( 22 – 24 ), the detailed costs and utilities were all displayed in Table 2 . 2.5 Sensitive analysis One-way sensitivity was utilized to evaluate the uncertainty of this model. The outcomes were displayed in the tornado diagram, which visually showed the influence of each parameter on the ICER. We conducted probabilistic sensitivity analysis to investigate the robustness of this model. We performed 1,000 Monte Carlo simulations with key parameters. The cost parameter was described by gamma distribution and the utility parameter was characterized by beta distribution. The cost-effectiveness acceptability curves and scatterplots illustrated the likelihood of Hypo-RT being cost-effective across the WTP threshold. 3 Results 3.1 Base case results The results of the base–case analysis are shown in Table 3 . For Hypo-RT, the mean cost and QALYs were $ 123,721.28 and 2.23, respectively, while for Con-RT, the mean cost and QALYs were $ 187,803.55 and 1.69, respectively. The decremental cost-effectiveness ratio (ICER) for Hypo-RT versus Con-RT was $ 118,848.20/QALY. Table 3 CEA results of base-case Parameters and distributions Outcomes of markov models Incremental changes Hypo-RT Con-RT Costs 123,721.28 187,803.55 -64,082.28 Drug costs 112,863.86 175,998.15 -63,134.29 Monitoring costs 9,596.98 7,298.03 2,298.95 AEs costs 1,801.99 1,627.73 174.26 Lys 3.29 2.54 0.76 Overall QALYs 2.23 1.69 0.54 Incremental cost per QALY gained -118,848.20 3.2 One-way sensitivity analysis As shown in Fig. 2 , the costs of the Hypo-RT and Con-RT strategies were largely driven by the total drug costs, which represent 92.73% of the total costs (91.22% of the total costs for hypo-RT, 93.71% for con-RT). 3.3 Probabilistic sensitivity analysis The PSA results are illustrated by the cost-effectiveness plane and the cost-effectiveness acceptability curves (Figs. 3 and 4 ). Each small dot represents the incremental cost and incremental QALY from one simulation. The probability that Hypo-RT is cost-effective (calculated as the proportion of Monte Carlo simulations that fall below a given WTP threshold) is plotted against a range of WTP thresholds. The results showed that Hypo-RT was dominant compared to Con-RT in 100.0% of 1,000 Monte Carlo iterations and was cost-effective at a WTP threshold of $ 12,621.19 (one time GDP in 2023) per QALY gained in 100.0% of iterations. The results favoured the cost-effectiveness of Hypo-RT in most of the scenarios. 3.4 Value of information analysis Probabilistic sensitivity analysis yielded an expected value of perfect information (EVPI) of 16,411 per patient at a WTP threshold of 65,000 per QALY (Fig. 5 ). The EVPI demonstrated threshold dependency, decreasing to 56,488 at a more conservative WTP threshold of 20,000/QALY. 3.4 Scenario analysis The price scenario analysis demonstrated that Hypo-RT remained cost-saving compared to Con-RT when the cost of Con-RT was reduced by 20% (Table 4 & Fig. 6 ). However, further reductions in the cost of Con-RT (30%, 40%, or 50%) shifted the economic outcome: Hypo-RT was no longer cost-saving but still yielded favorable incremental cost-effectiveness ratios (ICERs) of 21,505.31, 21,505.31, 44,816.62, and $ 68,127.94 per QALY gained, respectively, which was also much lower than 1 time of GDP, mean that Hypo-RT maintained a 100% probability of being cost-effective across all scenarios, even when Con-RT's price was significantly lowered (Table 4 & Fig. 6 ). Table 4 Scenario analysis results Percentages of Con-RT's Discount Total costs of Therapy Con-RT Incre-costs (Hypo-RT/Con-RT) 80% price of Con-RT 155,070.93 -31,349.66 70% price of Con-RT 112,125.73 11,595.54 60% price of Con-RT 99,556.40 24,164.87 50% price of Con-RT 86,987.08 36,734.20 4 Discussions To effectively allocate national healthcare resources, there is a growing emphasis on using pharmacoeconomic evidence to support decision-making, especially for new drugs that may have significant clinical benefits but could be more costly. According to data from the World Health Organization (WHO), millions of patients die from cancer worldwide each year, with lung cancer being a leading cause ( 31 ). NSCLC accounts for approximately 85% of all primary lung cancers ( 32 ). Stage III NSCLC, also called locally advanced NSCLC, accounts for 30% of NSCLC patients ( 33 ). Pharmacoeconomic evaluation provides more substantial, objective, comprehensive evidence and aids in long-term planning in areas such as public health and medical insurance. Among all types of NSCLC, unresectable stage III NSCLC is particularly challenging for patients. This is because many patients have smoking-related cardiac or respiratory comorbidities, which makes them unsuitable for surgery. Therefore, for these patients, radiotherapy is a safer and potentially curative option. The appearance of Hypo-RT significantly prolongs the PFS and OS of unresectable stage III NSCLC and its efficacy is further enhanced. Regrettably, high incidences of toxicity for Hypo-RT (radiation esophagitis, 14%-83.3%; RP, 3.3%-28.6%) were also reported ( 11 ). The current study was an economic evaluation with the target population of unresectable stage III NSCLC. The interventions evaluated were Hypo-RT, with Con-RT serving as the comparator. This study aimed to provide an answer to the question of whether the use of Hypo-RT and Con-RT in these patients was cost-effective. In this research, Hypo-RT resulted in 2.23 QALYs and an ICER of $ 118,848.20/QALY. The results indicated that Hypo-RT is the more cost-effective treatment modality compared with Con-RT alone for the treatment of patients with unresectable stage III non-small cell lung cancer. This study analyzed the cost-effectiveness of Hypo-RT and Con-RT treatments in unresectable stage III non-small cell lung. Thus, the current study had limitations, including assumptions, data sources, parameter estimations, and the structure of the model. Furthermore, the study extrapolated the PFS and OS curves through the fitting of parameter distributions. Although multiple measures were taken to ensure the rationality of the parametric distribution selected for data extrapolation, this increases the uncertainty of the model output and may lead to errors in the fitted data.Thirdly, a limitation that must be mentioned in relation to this study is that it only addresses the direct costs of unresectable stage III non-small cell lung, disregarding the burden of indirect costs, which can be predictably high. 5 Conclusions Based on a Markov model analysis from the Chinese healthcare system perspective, moderately Hypo-RT demonstrates cost-effectiveness compared with Con-RT for unresectable stage III non-small cell lung cancer patients receiving concurrent chemotherapy, with an incremental cost-effectiveness ratio of $ 118,848.20 per quality-adjusted life year gained. The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors. Abbreviations Non-small cell lung cancer (NSCLC) Moderately hypofractionated radiation therapy (Hypo-RT) Conventional radiation therapy (Con-RT) Quality-adjusted life year (QALY) Incremental cost-effectiveness ratio (ICER) Progression-free survival (PFS) Progressive disease (PD) Overall survival (OS) Life years (LYs) Adverse events (AEs) Gross domestic product (GDP) Willingness-to-pay (WTP) Akaike information criterion (AIC) Bayesian information criterion (BIC) Expected value of perfect information (EVPI) Magnetic Resonance Imaging (MRI) World Health Organization (WHO) Declarations Data availability statement The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Supplementary Files Supplementary.docx TABLE2Modelparameters.docx Cite Share Download PDF Status: Published Journal Publication published 29 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 14 Jul, 2025 Reviews received at journal 08 Jul, 2025 Reviews received at journal 28 Jun, 2025 Reviewers agreed at journal 26 Jun, 2025 Reviewers agreed at journal 26 Jun, 2025 Reviewers invited by journal 30 Apr, 2025 Editor assigned by journal 30 Apr, 2025 Editor invited by journal 30 Apr, 2025 Submission checks completed at journal 28 Apr, 2025 First submitted to journal 17 Apr, 2025 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-6470075","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":451241145,"identity":"74fed68a-79c6-4d23-b490-fd3f7bb1edc8","order_by":0,"name":"Hui Zhang","email":"","orcid":"","institution":"Guangdong Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Zhang","suffix":""},{"id":451241146,"identity":"7ada4c45-004a-4e39-9893-5ac99b6d3871","order_by":1,"name":"Yuhang Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACNvbmgw8+/qnh4WdvbHyQ8MOGsBY+nmPJhjMbjslI9hxuNnjYk0ZYi5xEjpk0ZwOzjcGN9DbJB2yHiXCYRFqCNOMONh6DMwfbKhJ4DjPwt3cn4NfC8/iAceEZGR7J441tNxIs0hkkzpzdgF8Le1pC8gw2Nh4+oC03EnisGQwkcgloYcgxOMzDxszDcCOxrSCBjZkILRw5hs28bcw8AkAtDAlszkRoAQYy44wzx3gkew42SyT2pPEQ9It8e/PxHx8qauz52dsffvzxw0aOv70XvxYMwEOa8lEwCkbBKBgFWAEAa+BMlKJbdjAAAAAASUVORK5CYII=","orcid":"","institution":"Guangdong Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Yuhang","middleName":"","lastName":"Liu","suffix":""},{"id":451241147,"identity":"725d504f-cc77-4c3e-8237-4a93359723ca","order_by":2,"name":"Guihao Zeng","email":"","orcid":"","institution":"Guangdong Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Guihao","middleName":"","lastName":"Zeng","suffix":""},{"id":451241148,"identity":"212db9bd-1fc9-43af-bba6-64f81f505a44","order_by":3,"name":"Shuangshuang Hu","email":"","orcid":"","institution":"Guangdong Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Shuangshuang","middleName":"","lastName":"Hu","suffix":""},{"id":451241149,"identity":"a57cb7f4-da60-4986-81a1-147881197c32","order_by":4,"name":"Haonan Li","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Haonan","middleName":"","lastName":"Li","suffix":""},{"id":451241150,"identity":"b6ea51fc-4f52-4cef-95cc-5acd6fb87ee2","order_by":5,"name":"Hong Wang","email":"","orcid":"","institution":"Guangdong Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-04-17 09:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6470075/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6470075/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-28781-1","type":"published","date":"2025-12-29T15:57:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82275134,"identity":"9fc95295-a187-4fff-9b93-d49e2fe2f374","added_by":"auto","created_at":"2025-05-08 14:38:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":119615,"visible":true,"origin":"","legend":"\u003cp\u003eMarkov model structure\u003c/p\u003e\n\u003cp\u003ePFS, progression-free survival; PD, progression disease\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/20f20cfc1360e7ca52d4a4ae.png"},{"id":82273682,"identity":"ec8cca05-5b14-48fe-a87d-7a85cfc0e53f","added_by":"auto","created_at":"2025-05-08 14:30:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":230168,"visible":true,"origin":"","legend":"\u003cp\u003eTornado program\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/255da23c464952e76e6b733a.png"},{"id":82272005,"identity":"86ba4598-72d5-4b7a-92e8-4c204d38237e","added_by":"auto","created_at":"2025-05-08 14:22:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":273752,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analysis\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/3abe1259cd2e5a7a24037f2c.png"},{"id":82272011,"identity":"d3c08279-90f5-4f23-8222-d54960e3a8f5","added_by":"auto","created_at":"2025-05-08 14:22:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":186619,"visible":true,"origin":"","legend":"\u003cp\u003eCost-effectiveness acceptability curve\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/cee8743d617cd9fd20ac0b78.png"},{"id":82272009,"identity":"1f907639-5193-4f08-b072-53a9a8906623","added_by":"auto","created_at":"2025-05-08 14:22:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":161919,"visible":true,"origin":"","legend":"\u003cp\u003eExcepted value of information\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/ac0e4724ced66f2169219fc6.png"},{"id":82273685,"identity":"6f77e27e-8366-4822-aefd-e799272cb237","added_by":"auto","created_at":"2025-05-08 14:30:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":143532,"visible":true,"origin":"","legend":"\u003cp\u003eScenario analysis results\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/d1f90fbb01601e698d33ba0d.png"},{"id":99545254,"identity":"5d0c99de-18dd-4701-bdcf-2dbbdd7efd85","added_by":"auto","created_at":"2026-01-05 16:04:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1839441,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/2e7d743e-253f-4895-b9dd-e6d4f5ed9abd.pdf"},{"id":82272007,"identity":"c0111c7d-22ad-4c28-85de-8746d0f4272d","added_by":"auto","created_at":"2025-05-08 14:22:03","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":89602,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/edd5ebe806ed8d24e8512d1b.docx"},{"id":82276360,"identity":"f0a49ab3-3a03-4a48-b873-a5fb1e85eb00","added_by":"auto","created_at":"2025-05-08 14:46:03","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":21787,"visible":true,"origin":"","legend":"","description":"","filename":"TABLE2Modelparameters.docx","url":"https://assets-eu.researchsquare.com/files/rs-6470075/v1/69d4362ca62da279ee5894df.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-effectiveness Analysis of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIn 2022, lung cancer accounted for approximately 2.5\u0026nbsp;million new diagnoses and 1.8\u0026nbsp;million deaths globally, representing the most prevalent cause of cancer-related morbidity and mortality. Non-small cell lung cancer (NSCLC) constituted 12.4% of all new cancer cases (1 in 8) and 18.7% of cancer deaths (1 in 5), imposing substantial physical, psychological, and socioeconomic burdens on affected individuals, their communities, and healthcare infrastructures worldwide (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The emergence of numerous novel medicines improves the survival outcomes of NSCLC. Nevertheless, the price of new medicines for individuals, which also significantly strains healthcare systems, especially in Northern America, Eastern Asia, and Northern Europe (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStage III NSCLC, also called locally advanced NSCLC, accounts for 30% of NSCLC patients (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Many of them have smoking-related cardiac or respiratory comorbidities that make them unfit for an operation. Historically, concurrent/sequential chemotherapy and radiation therapy (RT) with conventional fractionation of 60 Gy administered in 30 fractions was the standard treatment for patients with unresectable stage III NSCLC (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Although treatment paradigms for stage III NSCLC have evolved significantly from radiotherapy alone in the 1980s to contemporary concurrent chemoradiotherapy regimens, long-term outcomes remain unsatisfactory, with 5-year survival rates plateauing at 15\u0026ndash;20% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite the availability of curative-intent treatment strategies, surgery remains the standard-of-care for resectable, early-stage and functionally operable NSCLC (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Nevertheless, numerous patients suffer from smoking-related cardiac or respiratory comorbidities that render them unsuitable candidates for surgery. For such individuals, radiotherapy emerges as a safer and potentially curative alternative (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Historically, patients with inoperable early-stage NSCLC were treated with conventional radiation therapy (Con-RT).\u003c/p\u003e \u003cp\u003eBased on Con-RT, Hypofractionated-RT (Hypo-RT) has been developed in recent years. Hypo-RT is characterized by a high local dose of radiation given in fewer fractions as an ablative treatment, usually 60\u0026ndash;80 Gy in 3.0\u0026ndash;4.0 Gy fractions (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Both prospective and retrospective studies have demonstrated that, compared with Con-RT, Hypo-RT resulted in superior local control of the primary disease without an increase in major toxicity in patients with medically inoperable stage I NSCLC (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Therefore, Hypo-RT has emerged as a new technology in the treatment of NSCLC and has been gradually incorporated into clinical practice in China (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven the escalating prevalence of NSCLC and progressive cost burden associated with disease management, rigorous cost-effectiveness evaluations of novel therapies are imperative (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This analysis is based on data from the multicenter randomized phase 3 trial, which compared Hypo-RT (60 Gy/20 fractions) with Con-RT (60 Gy/30 fractions) in unresectable stage III NSCLC patients receiving concurrent chemotherapy. To our knowledge, this represents the first cost-effectiveness study of Hypo-RT in the Chinese context. Using a Markov decision-analytic model, we evaluate the economic value of Hypo-RT versus Con-RT, aiming to inform clinical practice and healthcare reimbursement policies.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 Patients and intervention\u003c/h2\u003e\n \u003cp\u003eThe enrolled patients were all derived from the randomized, multicentre, nonblinded phase 3 clinical trial. NSCLC patients with unresectable stage III non-small cell lung cancer were recruited. Patients were randomized at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). A total of 146 patients were enrolled and randomized at a 1:1 ratio: 73 to the Hypo-RT group (60 Gy in 20 fractions) and 73 to the Con-RT group (60 Gy in 30 fractions). Among these, 42 patients in the Hypo-RT group also received amivantamab-lazertinib. Hypo-RT was delivered at 3 Gy per fraction, while Con-RT was administered at 2 Gy per fraction, both on a Monday-to-Friday schedule. RT was delivered by Tomotherapy using a 6 MV beam in the Hypo-RT group and by IMRT (6\u0026ndash;18 MV) in the Con-RT group. All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eAll research methods were strictly conducted in accordance with relevant guidelines and regulations. This study was based on data from a multicenter randomized phase III clinical trial, which was approved by the Ethics Committee of Zhongshan Hospital (Approval No.: 2018ZSLC26). Written informed consent was obtained from all participants or their legal guardians before participation in the study.\u003c/p\u003e\n \u003cp\u003eIn our study, we assumed that the patients with a baseline weight of 70 kg, body surface area of 1.86 m\u003csup\u003e2\u003c/sup\u003e, and a creatinine clearance of 70 mL/min as standard (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e). Only when the grade of adverse events (AEs)\u0026thinsp;\u0026ge;\u0026thinsp;grade 3 (G3) in either the Hypo-RT or Con-RT group, AEs were identified for analysis. This study was carried out based on the phase 3 trial and did not involve other human participants. Hence, there is no need for the approval of the independent ethics committee.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Model construction\u003c/h2\u003e\n \u003cp\u003eA three-stage Markov model was established by the Microsoft Excel 2023 software, including PFS, progressive disease (PD), and death (Fig. 1). We extended the simulation period to 5 years, the simulated PFS and overall survival (OS) fitted with different distributions were displayed in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The simulation cycle duration was 3 weeks.\u003c/p\u003e\n \u003cp\u003eIn this study, a 3% annual discount rate was applied for future health utility and cost (\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e). The analysis included three key parameters: life years (LYs) total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs from previous years were adjusted using the consumer price index for healthcare of 2016\u0026ndash;2023 and were shown in 2023 US dollars (1 USD\u0026thinsp;=\u0026thinsp;7.08 CNY). A willingness-to-pay (WTP) threshold was set as the forecasted gross domestic product (GDP) per capita at \u003cspan\u003e$\u003c/span\u003e12,621.19 (￥89,358)-\u003cspan\u003e$\u003c/span\u003e37,863.51(￥268,074), which was taken from the Statistical Communiqu\u0026eacute; of the People\u0026rsquo;s Republic of China on the 2023 National Economic and Social Development. A treatment was considered cost-effective if its calculated ICER was lower than this established threshold (\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCost-effectiveness analytical framework\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComparator\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHypo-RT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCon-RT\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePopulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePatients with unresectable stage III non-small cell lung cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecision-analytical model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMarkov model\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDirect medical costs, quality-adjusted life-year, and incremental cost-effectiveness ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eProgression-free state, progressed-disease state, and death\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCycle length\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime horizon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiscount rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWillingness-to-pay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eForecasted gross domestic product per capita in 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMeasurements\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eICER, incremental cost-effectiveness ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScenario analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eGradual 10% price reduction of hypo-RT, using life-years to measure effectiveness, using second-best fit survival models, applying a conversion factor to nonmedication costs, and assuming adverse events incurred every cycle during the first six months and the entire time horizon.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3 Model survival and transition probabilities\u003c/h2\u003e\n \u003cp\u003eThe OS and PFS data of Hypo-RT and Con-RT were extracted by the GetData Graph Digitizer. The estimates of the OS curve and PFS curve for all groups were reconstructed by R software. A series of statistical distributions, such as the Log-logistic, Log-normal, Weibull, Gompertz, Exponential, and Gamma distributions were utilized to fit the pseudo-individual patient data set. This study chose the most suitable survival function with the lowest Akaike information criterion (AIC) and Bayesian information criterion values (BIC) (\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e). Detailed model diagnostics were presented in Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The shape parameter (\u0026lambda;) and the scale parameter (\u0026gamma;) of the suitable function were gained from R software.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.4 Cost and utility estimates\u003c/h2\u003e\n \u003cp\u003eFrom the perspective of the healthcare system, our research only focused on the direct medical costs, including the cost of radiotherapy, the cost of chemotherapy, the drug costs, the costs of adverse effect managements, the cost of monthly best supportive care, the cost of abdomen enhanced CT, the cost of chest enhanced CT and the cost of MRI. AEs were considered to include grade\u0026thinsp;\u0026ge;\u0026thinsp;3 adverse events: acute radiation pneumonitis (RP), leukopenia, anemia, late RP, late RE, and platelet count decreased. related treatment costs were derived from the published literature, and on this basis, opinions of clinical experts were considered (including 23 clinical experts from more than 11 grade A tertiary hospitals in 3 provinces in China). Monitoring frequencies of unresectable stage III NSCLC were driven from drug package inserts and the CSCO Guidelines for NSCLC (2023) (\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eQALYs were used to assess the effectiveness of each health condition. The utilities of PFS and PD in our model were 0.81 and 0.67 (\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e). To evaluate the negative effect of AEs, the disutility of AEs was also considered in this model (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e), the detailed costs and utilities were all displayed in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e2.5 Sensitive analysis\u003c/h2\u003e\n \u003cp\u003eOne-way sensitivity was utilized to evaluate the uncertainty of this model. The outcomes were displayed in the tornado diagram, which visually showed the influence of each parameter on the ICER.\u003c/p\u003e\n \u003cp\u003eWe conducted probabilistic sensitivity analysis to investigate the robustness of this model. We performed 1,000 Monte Carlo simulations with key parameters. The cost parameter was described by gamma distribution and the utility parameter was characterized by beta distribution. The cost-effectiveness acceptability curves and scatterplots illustrated the likelihood of Hypo-RT being cost-effective across the WTP threshold.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Base case results\u003c/h2\u003e \u003cp\u003eThe results of the base\u0026ndash;case analysis are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. For Hypo-RT, the mean cost and QALYs were \u003cspan\u003e$\u003c/span\u003e123,721.28 and 2.23, respectively, while for Con-RT, the mean cost and QALYs were \u003cspan\u003e$\u003c/span\u003e187,803.55 and 1.69, respectively. The decremental cost-effectiveness ratio (ICER) for Hypo-RT versus Con-RT was \u003cspan\u003e$\u003c/span\u003e118,848.20/QALY.\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 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCEA results of base-case\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\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters and distributions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eOutcomes of markov models\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIncremental changes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypo-RT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCon-RT\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCosts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123,721.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187,803.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-64,082.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug costs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112,863.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175,998.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-63,134.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonitoring costs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,596.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,298.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,298.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAEs costs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,801.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,627.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e174.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLys\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall QALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eIncremental cost per QALY gained\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-118,848.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 One-way sensitivity analysis\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the costs of the Hypo-RT and Con-RT strategies were largely driven by the total drug costs, which represent 92.73% of the total costs (91.22% of the total costs for hypo-RT, 93.71% for con-RT).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Probabilistic sensitivity analysis\u003c/h2\u003e \u003cp\u003eThe PSA results are illustrated by the cost-effectiveness plane and the cost-effectiveness acceptability curves (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Each small dot represents the incremental cost and incremental QALY from one simulation. The probability that Hypo-RT is cost-effective (calculated as the proportion of Monte Carlo simulations that fall below a given WTP threshold) is plotted against a range of WTP thresholds. The results showed that Hypo-RT was dominant compared to Con-RT in 100.0% of 1,000 Monte Carlo iterations and was cost-effective at a WTP threshold of \u003cspan\u003e$\u003c/span\u003e12,621.19 (one time GDP in 2023) per QALY gained in 100.0% of iterations. The results favoured the cost-effectiveness of Hypo-RT in most of the scenarios.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Value of information analysis\u003c/h2\u003e \u003cp\u003eProbabilistic sensitivity analysis yielded an expected value of perfect information (EVPI) of 16,411 per patient at a WTP threshold of 65,000 per QALY (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The EVPI demonstrated threshold dependency, decreasing to 56,488 at a more conservative WTP threshold of 20,000/QALY.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Scenario analysis\u003c/h2\u003e \u003cp\u003eThe price scenario analysis demonstrated that Hypo-RT remained cost-saving compared to Con-RT when the cost of Con-RT was reduced by 20% (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e). However, further reductions in the cost of Con-RT (30%, 40%, or 50%) shifted the economic outcome: Hypo-RT was no longer cost-saving but still yielded favorable incremental cost-effectiveness ratios (ICERs) of 21,505.31, 21,505.31, 44,816.62, and \u003cspan\u003e$\u003c/span\u003e68,127.94 per QALY gained, respectively, which was also much lower than 1 time of GDP, mean that Hypo-RT maintained a 100% probability of being cost-effective across all scenarios, even when Con-RT's price was significantly lowered (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eScenario analysis results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercentages of Con-RT's Discount\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal costs of Therapy Con-RT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncre-costs (Hypo-RT/Con-RT)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e80% price of Con-RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155,070.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-31,349.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70% price of Con-RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112,125.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,595.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60% price of Con-RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99,556.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24,164.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50% price of Con-RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86,987.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36,734.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussions","content":"\u003cp\u003eTo effectively allocate national healthcare resources, there is a growing emphasis on using pharmacoeconomic evidence to support decision-making, especially for new drugs that may have significant clinical benefits but could be more costly. According to data from the World Health Organization (WHO), millions of patients die from cancer worldwide each year, with lung cancer being a leading cause (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). NSCLC accounts for approximately 85% of all primary lung cancers (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Stage III NSCLC, also called locally advanced NSCLC, accounts for 30% of NSCLC patients (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Pharmacoeconomic evaluation provides more substantial, objective, comprehensive evidence and aids in long-term planning in areas such as public health and medical insurance.\u003c/p\u003e \u003cp\u003eAmong all types of NSCLC, unresectable stage III NSCLC is particularly challenging for patients. This is because many patients have smoking-related cardiac or respiratory comorbidities, which makes them unsuitable for surgery. Therefore, for these patients, radiotherapy is a safer and potentially curative option. The appearance of Hypo-RT significantly prolongs the PFS and OS of unresectable stage III NSCLC and its efficacy is further enhanced. Regrettably, high incidences of toxicity for Hypo-RT (radiation esophagitis, 14%-83.3%; RP, 3.3%-28.6%) were also reported (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe current study was an economic evaluation with the target population of unresectable stage III NSCLC. The interventions evaluated were Hypo-RT, with Con-RT serving as the comparator. This study aimed to provide an answer to the question of whether the use of Hypo-RT and Con-RT in these patients was cost-effective. In this research, Hypo-RT resulted in 2.23 QALYs and an ICER of \u003cspan\u003e$\u003c/span\u003e118,848.20/QALY. The results indicated that Hypo-RT is the more cost-effective treatment modality compared with Con-RT alone for the treatment of patients with unresectable stage III non-small cell lung cancer.\u003c/p\u003e \u003cp\u003eThis study analyzed the cost-effectiveness of Hypo-RT and Con-RT treatments in unresectable stage III non-small cell lung. Thus, the current study had limitations, including assumptions, data sources, parameter estimations, and the structure of the model. Furthermore, the study extrapolated the PFS and OS curves through the fitting of parameter distributions. Although multiple measures were taken to ensure the rationality of the parametric distribution selected for data extrapolation, this increases the uncertainty of the model output and may lead to errors in the fitted data.Thirdly, a limitation that must be mentioned in relation to this study is that it only addresses the direct costs of unresectable stage III non-small cell lung, disregarding the burden of indirect costs, which can be predictably high.\u003c/p\u003e"},{"header":"5 Conclusions","content":"\u003cp\u003eBased on a Markov model analysis from the Chinese healthcare system perspective, moderately Hypo-RT demonstrates cost-effectiveness compared with Con-RT for unresectable stage III non-small cell lung cancer patients receiving concurrent chemotherapy, with an incremental cost-effectiveness ratio of \u003cspan\u003e$\u003c/span\u003e118,848.20 per quality-adjusted life year gained.\u003c/p\u003e\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNon-small cell lung cancer (NSCLC)\u003c/p\u003e\n\u003cp\u003eModerately hypofractionated radiation therapy (Hypo-RT)\u003c/p\u003e\n\u003cp\u003eConventional radiation therapy (Con-RT)\u003c/p\u003e\n\u003cp\u003eQuality-adjusted life year (QALY)\u003c/p\u003e\n\u003cp\u003eIncremental cost-effectiveness ratio (ICER)\u003c/p\u003e\n\u003cp\u003eProgression-free survival (PFS)\u003c/p\u003e\n\u003cp\u003eProgressive disease (PD)\u003c/p\u003e\n\u003cp\u003eOverall survival (OS)\u003c/p\u003e\n\u003cp\u003eLife years (LYs)\u003c/p\u003e\n\u003cp\u003eAdverse events (AEs)\u003c/p\u003e\n\u003cp\u003eGross domestic product (GDP)\u003c/p\u003e\n\u003cp\u003eWillingness-to-pay (WTP)\u003c/p\u003e\n\u003cp\u003eAkaike information criterion (AIC)\u003c/p\u003e\n\u003cp\u003eBayesian information criterion (BIC)\u003c/p\u003e\n\u003cp\u003eExpected value of perfect information (EVPI)\u003c/p\u003e\n\u003cp\u003eMagnetic Resonance Imaging (MRI)\u003c/p\u003e\n\u003cp\u003eWorld Health Organization (WHO)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. Doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.\u003c/li\u003e\n\u003cli\u003eXing M, Liu H, Tong L, et al. Learning curve for double micro-portal video-assisted thoracoscopic lobectomy. Journal of Thoracic Disease, 2025, 17(1). Doi: 10.21037/jtd-24-1000.\u003c/li\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2024, 74(3): 229-263. Doi: 10.3322/caac.21834.\u003c/li\u003e\n\u003cli\u003eChinese Anti-Cancer Association. Chinese expert consensus on the multidisciplinary clinical diagnosis and treatment of stage Ⅲ non-small cell lung cancer (2019). Chinese Journal of Oncology, 2019, 41(12): 881-890. 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Wisnivesky. \u0026quot;Global epidemiology of lung cancer.\u0026quot; Annals of global health 85.1 (2019). Doi: 1016/j.soc.2016.02.001.\u003c/li\u003e\n\u003cli\u003eIlie, Marius, and Paul Hofman. \u0026quot;Atezolizumab in advanced non-small cell lung cancer.\u0026quot; Journal of thoracic disease 9.10 (2017): 3603. Doi: 10.21037/jtd.2017.09.73.\u003c/li\u003e\n\u003cli\u003eMajem, Margarita, et al. \u0026quot;Multidisciplinary consensus statement on the clinical management of patients with stage III non-small cell lung cancer.\u0026quot; Clinical and Translational Oncology 22 (2020): 21-36. Doi: 10.1007/s12094-019-02134-7.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 2","content":"\u003cp\u003eTable 2 is available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"non-small cell lung cancer, cost-effectiveness analysis, hypofractionated radiation therapy, conventional radiation therapy","lastPublishedDoi":"10.21203/rs.3.rs-6470075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6470075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e Moderately Hypofractionated Radiation Therapy (Hypo-RT) has been considered as an alternative strategy for unresectable stage III non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy, with potential benefits in overall survival and local control. In this study, we compared the cost-effectiveness of Hypo-RT with that of Con-RT in patients with unresectable stage III non-small cell lung cancer receiving concurrent chemotherapy.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eBoth prospective and retrospective studies have demonstrated that, compared with Con-RT, Hypo-RT resulted in superior local control of the primary disease without an increase in major toxicity in patients with medically inoperable stage III NSCLC. However, to the best of our knowledge, the economic value of using this new therapy for this indication is currently unknown. Therefore, our study aimed to evaluate the cost-effectiveness of Hypo-RT for the standard-of-care treatment of medically inoperable, early-stage NSCLC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA three-stage Markov model over a 5-year lifetime horizon was developed to compare the cost and effectiveness of Hypo-RT with that of Con-RT. The primary outcomes of our study included life years (LYs) total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the base case analysis, the cost and QALYs of Hypo-RT were \u003cspan\u003e$\u003c/span\u003e123,721.28 and 2.23, while for Con-RT, the cost and QALYs were \u003cspan\u003e$\u003c/span\u003e187,803.55 and 1.69, respectively. Hypo-RT is a more cost-effective strategy compared with Con-RT for medically inoperable stage III NSCLC, with \u003cspan\u003e$\u003c/span\u003e118,848.20 is saved for every incremental QALY. This result was validated by DSA and PSA, in which SBRT remained the most cost-effective option. Hypo-RT was dominant compared to Con-RT, and Hypo-RT was the most cost-effective option.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHypo-RT is likely to be a cost-effective option compared with Con-RT for patients with unresectable stage III non-small cell lung cancer receiving concurrent chemotherapy.\u003c/p\u003e","manuscriptTitle":"Cost-effectiveness Analysis of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-08 14:21:58","doi":"10.21203/rs.3.rs-6470075/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-14T07:27:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-08T04:51:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-28T15:25:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140486221216033624630481853030506157701","date":"2025-06-26T22:16:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84223067877188635480944523171934075213","date":"2025-06-26T13:07:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-30T05:29:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-30T05:26:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-30T04:51:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-28T08:00:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-17T09:04:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a8bd59f-6dcf-4af0-b0be-3e2f1c12b7cf","owner":[],"postedDate":"May 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48009794,"name":"Biological sciences/Drug discovery/Pharmacology/Clinical pharmacology"},{"id":48009795,"name":"Biological sciences/Drug discovery/Pharmacology/Pharmacodynamics"}],"tags":[],"updatedAt":"2026-01-05T15:59:40+00:00","versionOfRecord":{"articleIdentity":"rs-6470075","link":"https://doi.org/10.1038/s41598-025-28781-1","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-29 15:57:21","publishedOnDateReadable":"December 29th, 2025"},"versionCreatedAt":"2025-05-08 14:21:58","video":"","vorDoi":"10.1038/s41598-025-28781-1","vorDoiUrl":"https://doi.org/10.1038/s41598-025-28781-1","workflowStages":[]},"version":"v1","identity":"rs-6470075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6470075","identity":"rs-6470075","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}