Surrogate Marker Research Articles

Temporalis muscle thickness as a predictor of functional outcome after reperfusion therapies for acute ischemic stroke: a retrospective, cohort study.

Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3months represented the main endpoint of functional outcome. A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0-1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538-0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease.

Contraceptive efficacy: Determining the threshold for effective suppression based on sperm concentration, motility, and morphology.

Human spermatogenesis is a complex process that transforms spermatogonial stem cells through mitosis and meiosis to spermatozoa. Testosterone is the key regulator of the terminal stages of meiosis, adherence of spermatids to Sertoli cells, and spermiation. Follicle-stimulating hormone (FSH) may be required for early spermatogenesis and is important for maintaining normal spermatogenesis in men. Hormonal contraception suppresses FSH, luteinizing hormone, and intratesticular testosterone concentration, resulting in marked suppression of sperm output. Clinical trials using testosterone alone or testosterone plus progestin demonstrate that sustained suppression of sperm concentration to ≤1 million/mL is sufficient to prevent pregnancy in the female partner. New agents that target spermatogenesis could use this as a target for contraceptive efficacy while others that block sperm function or transport may require a lower threshold. When sperm concentrations are suppressed to such low levels, measurement of sperm motility and morphology is technically difficult and unnecessary. With current data from fertile and infertile men, it is not possible to establish a lower limit of sperm motility or percent normal morphology that equates to the prevention of conception. New compounds that decrease sperm motility or alter sperm morphology may need to demonstrate a complete absence of sperm motility or altered morphology in all spermatozoa in the ejaculate. Sperm function tests may be useful depending on the mechanism of action of each new compound. Monitoring of sperm surrogate markers to ensure effective contraception relies on laboratories experienced in semen analyses. The development of at-home tests to assess sperm parameters has progressed rapidly. Some tests have been assessed in clinical trials and approved by regulatory agencies for at-home use for fertility assessment. However, caution must be exercised in using these tests as many have not been rigorously validated against semen parameters measured in laboratories by trained technologists using standardized tests defined in the World Health Organization Semen Manual.

Human papillomavirus-associated head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting strategies are desperately needed, and a previous report indicated the triggered differentiation of HPV-negative HNSCC cells to confer therapeutic benefits. Using patient-derived tumor cells, we created a similar HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-Seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like in vitro differentiation occurs in human tissue. We are the first to report that carcinoma cells can undergo a triggered myocyte-like differentiation, and our study suggests that the targeted differentiation of HPV+ HNSCCs might be therapeutically valuable.

Hepatitis C Virus Reinfection Among Men Who Have Sex With Men With HIV in New York City.

Hepatitis C virus (HCV) reinfection rates are substantially higher than primary infection rates among men who have sex with men (MSM) with human immunodeficiency virus (HIV) in European cohorts. The behaviors mediating this high rate of transmission among MSM are poorly characterized. We performed a prospective cohort study in New York City (NYC) of MSM with HIV who cleared HCV to determine the incidence of and risk factors for HCV reinfection. We assessed the risk behaviors for primary HCV in NYC: receipt of semen in the rectum, and sexualized methamphetamine use, along with route of use. Multivariable analysis was performed with Andersen-Gill extension of the Cox proportional hazards model. From 2000 through 2018, among 304 MSM with HIV who cleared HCV, 42 reinfections occurred over 898 person-years, for an incidence rate of 4.7 per 100 person-years. Assessing 1245 postclearance visits, only receipt of semen into the rectum was associated with reinfection (hazard ratio, 9.7 [95% confidence interval: 3.3-28.3], P < .001); methamphetamine use was not. The high HCV reinfection rate over almost 2 decades demonstrates that sexual transmission of HCV is not inefficient or unusual and that direct-acting antiviral treatment is not sufficient for HCV elimination among MSM in NYC. The contrasts between both the rates of and risk factors for primary and HCV reinfection suggest that HCV prevalence is highly heterogenous among sexual networks and that sexualized methamphetamine use, rather than mediating transmission, is instead a surrogate marker for the highest HCV prevalence networks. As neither condoms nor treatment have been successful strategies for HCV prevention in NYC, novel interventions are needed to stem this sexually transmitted HCV epidemic.

Plasma B-type natriuretic peptide is independently associated with cardiovascular events and mortality in patients with chronic kidney disease

The association between B-type natriuretic peptide (BNP) and cardiovascular (CV) events and mortality has not been well characterized in patients with chronic kidney disease (CKD). We prospectively investigated whether BNP was associated with CV events or mortality beyond cardiac alterations in 1078 patients with CKD. Participants were divided into the following 3 groups according to circulating BNP concentration: < 40 pg/mL, low; 40–100 pg/mL, middle; and > 100 pg/mL, high. Primary outcome was fatal or nonfatal CV events, and alternative outcome was a composite of fatal or nonfatal CV events, or non-CV deaths. During a median follow-up of 2.6 years, CV and composite events occurred in 158 and 248 participants, respectively. Cox analyses after adjustment for covariates, including cardiac parameters, showed that the hazard ratios (HRs) (95% confidence intervals [CIs]) for CV events of middle and high groups were 1.00 (0.63, 1.58) and 1.72 (1.06, 2.79), respectively, compared with low group. Additionally, similar results were obtained for composite events; the HRs (95% CIs) of middle and high groups were 1.10 (0.77, 1.57) and 1.54 (1.04, 2.27), respectively, compared with low group. Thus, in CKD, high BNP concentrations were independently associated with CV events and mortality, independent of cardiac alterations.

Role of Echocardiographic Aortic Propagation Velocity in Predicting Obstructive Coronary Artery Disease – A Prospective Observational Study

Objectives: The aim of this study was to assess the relationship between APV and CAD and to compare AS and AD in patients with and without CAD. Material and Methods: A total of 100 subjects presenting to Government General Hospital, Guntur, with chest pain and undergoing coronary angiogram were selected for the study. Patients were divided into two groups, the study group comprises patients with &gt;50% stenosis in at least one of the coronary artery on coronary angiogram, and control group comprises patients with normal coronaries on angiography. Two-dimensional echocardiography (Philips Affinity 70) was performed with the recording of data. AS and AD were calculated and APV was determined. Result: In the present study, it was observed that there was a statistically significant increased incidence of deranged lipid profile, diabetes, hypertension, alcohol consumption, and a positive family history of CAD in the study group. Mean APV, mean AD, and mean AS was significantly low in the study group as compared to the control group (P &lt; 0.001). Conclusion: APV, AS, and AD can be used as surrogate marker to predict the presence of significant CAD and, hence, can be safely recommended as a simple, economical, and non-invasive means to screen CAD.

Transcriptomic analysis of the human habenula in schizophrenia.

Transcriptomic analysis of the human habenula and identification of molecular changes associated with schizophrenia risk and illness state.

Postoperative prognostic nutrition index predicts survival in patients with small bowel adenocarcinoma after surgical resection.

Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. This study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection. From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed. PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI < 45.2 best predicted overall survival (OS) (AUROC: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those higher postoperative values (median OS: 19.3 months vs. not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001). PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.

Developing quantitative analysis program of blood flow velocity according to vessel diameter for neovascular age-related macular degeneration using OCTA-VISTA

This study aimed to develop a quantitative analysis program of blood flow velocity by vessel diameter in neovascular age-related macular degeneration (nAMD) subjects using high-speed swept-source optical coherence tomography angiography. This retrospective, observational, cross-sectional study included 10 eyes of healthy volunteers and 4 eyes of patients with representative nAMD. Novel scan patterns and variable interscan time analysis were utilized to measure the flow parameter, a surrogate marker of blood flow velocity, by vessel diameter within different depths. Detected vessels at superficial and deep as well as outer retinal regions were categorized into three vessel diameters (major vessels (> 40 μm), medium vessels (20–40 μm), and capillaries (< 20 μm)). The flow parameter increased with enlarged vessel diameter in all participants at superficial and deep layer. All nAMD subjects, except for type 3 macular neovascularization (MNV), contained a structure dominated by medium vessels at outer retinal region. The mean flow parameter at outer retinal region was type 1 MNV (1.46 ms−1), type 1 + 2 MNV (0.98 ms−1), and polypoidal choroidal vasculopathy, including branching vascular networks (1.46 ms−1). This program provides the possibility to extract the blood flow information at different depths by vessel diameter types, which is considered to be useful tool for evaluating nAMD pathology and activity.

A Unique Comprehensive Model to Screen Newborns for Severe Combined Immunodeficiency-An Ontario Single-Centre Experience Spanning 2013-2023.

Severe combined immunodeficiency (SCID) is a life-threatening genetic disorder caused by critical defects of the immune system. Almost all cases are lethal if not treated within the first two years of life. Early diagnosis and intervention are thus essential for improving patient outcomes. In 2013, Ontario became the first Canadian province to perform newborn screening (NBS) for SCID by T cell receptor excision circles (TRECs) analysis, a surrogate marker of thymic function and lymphocyte maturation. This retrospective study reports on nearly 10 years of NBS for SCID at a quaternary referral centre. From August 2013 to April 2023, our centre's densely populated catchment area flagged 162 newborns with low TRECs levels, including 10 cases with SCID. Follow-up revealed other causes of low TRECs, including non-SCID T cell lymphopenia (secondary/reversible or idiopathic causes, and syndromic conditions) and prematurity. A small number of cases with normal repeat TRECs levels and/or T cell subsets were also flagged. Province-wide data from around this period revealed at least 24 diagnosed cases of SCID or Leaky SCID. This is the first report of NBS outcomes in a Canadian province describing the causative genetic defects, and the non-SCID causes of a positive NBS for SCID.

Replaying the Tape of Academia: Fourteen Alternative Practices for the Physical Sciences

AbstractThe evolution of modern academic practices, analogous to the evolution of biological systems, reflects the influence of both contingency and determinism. From a theoretical perspective, how then could academic practices differ from those that were inherited? Would any alternative outcomes be more just, equitable, diverse, or inclusive? Here we present 14 alternative academic practices that might be attained upon replaying the tape of academia and evaluate their benefits and drawbacks. Oriented primarily around the physical sciences within the United States, these alternative practices reconsider common activities within the broad categories of the graduate student experience, faculty careers, evaluation methods, peer review and publication, and conference norms. Consideration of these alternative practices can guide within‐system change and large‐scale restructuring of academia to address the myriad challenges facing researchers and students. Conversely, alternative practices may introduce new issues or exacerbate existing problems. These alternative practices are meant to be imaginative, not prescriptive, and we hope their underlying ideas spur reflection and conversation on the existing practices embedded within academic culture. Readers are encouraged to complete a brief survey regarding their impressions of the alternative practices, available at the following link: rebrand.ly/AlternativePractices2024.

A class of chemical compounds enhances clustering of muscle nicotinic acetylcholine receptor in cultured myogenic cells

Neuromuscular signal transmission is affected in various diseases including myasthenia gravis, congenital myasthenic syndromes, and sarcopenia. We used an ATF2-luciferase system to monitor the phosphorylation of MuSK in HEK293 cells introduced with MUSK and LRP4 cDNAs to find novel chemical compounds that enhanced agrin-mediated acetylcholine receptor (AChR) clustering. Four compounds with similar chemical structures carrying benzene rings and heterocyclic rings increased the luciferase activities 8- to 30-folds, and two of them showed continuously graded dose dependence. The effects were higher than that of disulfiram, a clinically available aldehyde dehydrogenase inhibitor, which we identified to be the most competent preapproved drug to enhance ATF2-luciferase activity in the same assay system. In C2C12 myotubes, all the compounds increased the area, intensity, length, and number of AChR clusters. Three of the four compounds increased the phosphorylation of MuSK, but not of Dok7, JNK. ERK, or p38. Monitoring cell toxicity using the neurite elongation of NSC34 neuronal cells as a surrogate marker showed that all the compounds had no effects on the neurite elongation up to 1 μM. Extensive docking simulation and binding structure prediction of the four compounds with all available human proteins using AutoDock Vina and DiffDock showed that the four compounds were unlikely to directly bind to MuSK or Dok7, and the exact target remained unknown. The identified compounds are expected to serve as a seed to develop a novel therapeutic agent to treat defective NMJ signal transmission.

Putting the Asymmetric Response Concept to the test: Modeling multiple stressor exposure and release in a stream food web

Communities in stream ecosystems often respond asymmetrically to increase and release of stressors, as indicated by slow and incomplete recovery. The Asymmetric Response Concept (ARC) posits that this is due to a shift in the relative importance of three mechanisms: tolerance, dispersal, and biotic interactions. In complex natural communities, these mechanisms may produce alternative outcomes through poorly understood indirect effects. To understand how the three mechanisms respond to different temporal stressor scenarios, we studied multiple scenarios using a stream food web model. We asked the following questions: Do groups of species decline as expected on the basis of individual tolerance rankings derived from laboratory experiments when they are embedded in a complex dynamic food web? Does the response of ecosystem function match that of communities? To address these questions, we aggregated data on individual tolerances at the level of functional groups and studied how single and multiple stressors affect food web dynamics and nutrient cycling. Multiple stressor scenarios involved different intensities of salt and temperature increase. Functional groups exhibited a different relative tolerance ranking between the laboratory and dynamic food web contexts. Salt as a single stressor had only minor and transient effects at low level but led to the loss of one or more functional groups at high level. In contrast, high temperature, alone or in combination with salt, caused the loss of functional groups at all tested levels. Patterns often differed between the response of communities and ecosystem function. We discuss our findings with respect to the ARC.

Evidence for the Role of the Mitochondrial ABC Transporter MDL1 in the Uptake of Clozapine and Related Molecules into the Yeast Saccharomyces cerevisiae.

Clozapine is an antipsychotic drug whose accumulation in white cells can sometimes prove toxic; understanding the transporters and alleles responsible is thus highly desirable. We used a strategy in which a yeast (Saccharomyces cerevisiae) CRISPR-Cas9 knock-out library was exposed to cytotoxic concentrations of clozapine to determine those transporters whose absence made it more resistant; we also recognised the structural similarity of the fluorescent dye safranin O (also known as safranin T) to clozapine, allowing it to be used as a surrogate marker. Strains lacking the mitochondrial ABC transporter MDL1 (encoded by YLR188W) showed substantial resistance to clozapine. MDL1 overexpression also conferred extra sensitivity to clozapine and admitted a massive increase in the cellular and mitochondrial uptake of safranin O, as determined using flow cytometry and microscopically. Yeast lacking mitochondria showed no such unusual accumulation. Mitochondrial MDL1 is thus the main means of accumulation of clozapine in S. cerevisiae. The closest human homologue of S. cerevisiae MDL1 is ABCB10.

Heart rate variability as a predictor of intraoperative autonomic nervous system homeostasis.

The aim of the proof-of-concept study is to investigate the level of concordance between the heart rate variability (HRV), the EEG-based Narcotrend Index as a surrogate marker for the depth of hypnosis, and the minimal alveolar concentration (MAC) of the inhalation anesthetic sevoflurane across the entire course of a surgical procedure. This non-blinded cross-sectional study recorded intraoperative HRV, Narcotrend Index, and MAC in 31 male patients during radical prostatectomy using the Da-Vinci robotic-assisted surgical system at Mannheim University Medical Center. The degree of concordance was calculated using repeated measures correlation with the R package (rmcorr) and presented using the rmcorr coefficient (rrm). The Narcotrend Index correlates significantly across all measures with the time-dependent parameter of HRV, the standard deviation of the means of RR intervals (SDNN) (rrm = 0.2; p < 0.001), the frequency-dependent parameters low frequency (LF) (rrm = 0.09; p = 0.04) and the low frequency/high frequency ratio (LF/HF ratio) (rrm = 0.11; p = 0.002). MAC correlated significantly negatively with the time-dependent parameter of heart rate variability, SDNN (rrm = -0.28; p < 0.001), the frequency-dependent parameter LF (rrm = -0.06; p < 0.001) and the LF/HF ratio (rrm = -0.18; p < 0.001) and the Narcotrend Index (rrm = -0.49; p < 0.001) across all measures. HRV mirrors the trend of the Narcotrend Index used to monitor depth of hypnosis and the inhibitory influence of the anesthetic sevoflurane on the autonomic nervous system. Therefore, HRV can provide essential information about the homeostasis of the autonomic nervous system during general anesthesia. DRKS00024696, March 9th, 2021.

Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment.

Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence (mIF) analyses on tissue microarrays (n=3) from malignant peritoneal (MPeM, n=25) and pleural (MPM, n=88) mesothelioma patients. Our study aimed to elucidate spatial distributions of key immune cell populations and their association with LAG3, BAP1, NF2, and MTAP, with MTAP serving as a CDKN2A/B surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical characteristics. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared to MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared to those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma (https://mesotheliomaspatialatlas.streamlit.app/), containing mIF and hematoxylin and eosin (H&E) images.

Observational study of missing SOFA score data frequency in RCTs relative to ICU length of stay

The Sequential Organ Failure Assessment, also known as SOFA score, was introduced to assess organ dysfunction of critical ill patients. However, understanding the impact of missing SOFA scores in randomized controlled trials and how this affect the validity and applicability of the SOFA score as a surrogate endpoint for predicting mortality has been a matter of interest. To address this, a secondary analysis of a systematic review was conducted to quantify the relationship between SOFA scores and the prediction of mortality in critically ill adults in randomized controlled trials (RCTs). The systematic review being referred to included 87 RCTs with a total of 12,064 critically ill patients. This analysis focused on missing SOFA score data in relation to the length of stay on the intensive care unit (ICU) and the methods used to handle missing data. SOFA score measurements from the included studies were categorized into three time frames: Early (t ≤ 4 days), Intermediate (t = 5–10 days) and Late (t > 10 days) measurement. Only one study reported a complete data set for calculating the SOFA score for an Early measurement. When considering all methods used to address missing data, 32% of studies still had missing data for Early measurements, and this percentage increased to 64% for Late measurements. These findings suggested that, over time, the number of studies with incomplete data sets has been increasing. The longer a patient is treated on the ICU, the higher the number of missing data which can impact the validity of SOFA score analyses. There was no clear trend towards a specific method for compensating missing data. An exemplary calculation demonstrated that ignoring missing data may lead to an underestimated variability of the treatment effect. This, in turn, could bias the interpretation of study results by policy- and clinical decision-makers. Overall, there are several limitations that need to be considered when using SOFA score as a surrogate endpoint for mortality. When employed as an outcome, the SOFA score is frequently missing and most studies do not adequately describe the amount or nature of missing data, or the methods used to handle missing data in the analysis.

Phase Angle as Surrogate Marker of Muscle Weakness in Kidney Transplant Candidates Referred to Prehabilitation.

Phase angle (PhA), a marker of nutritional status obtained by bioelectrical impedance analysis (BIA), is associated with the integrity of cell membranes. Damage to muscle fiber membranes can impact muscle strength, which is related to adverse outcomes in adults with advanced chronic kidney disease (CKD). The main objective of this study was to determine the usefulness of the PhA in identifying muscle weakness in candidates for kidney transplants (KTs). Secondly, it aimed to examine the associations of PhA with other parameters of body composition, exercise performance, and muscle structure. Sensitivity, specificity, and area under the receiver operating characteristics curve were used to evaluate the PhA (index test) as a biomarker of muscle weakness. Muscle strength was estimated with maximal voluntary isometric contraction of the quadriceps (MVCI-Q) of the dominant side. Muscle weakness was defined as MVIC-Q < 40% of body weight. A total of 119 patients were evaluated (mean age 63.7 years, 75.6% men). A phase angle cut-off of 5.1° was identified to classify men with a higher likelihood of having low muscle strength in upper limbs (MVIC-Q 40% of their body weight). Male KT candidates with PhA < 5.1° had poorer exercise capacity, lower muscle strength, less muscle mass, and smaller muscle size. A PhA < 5.1° was significantly associated with an eight-fold higher muscle weakness risk (OR = 8.2, 95%CI 2.3-29.2) in a binary regression model adjusted by age, frailty, and hydration status. Remarkably, PhA is an easily obtainable objective parameter in CKD patients, requiring no volitional effort from the individual. The associations of PhA with aerobic capacity, physical activity, muscle mass, and muscle size underscore its clinical relevance and potential utility in the comprehensive evaluation of these patients.

Health-related quality of life outcomes reporting associated with FDA approvals in haematology and oncology

ObjectiveHealth-related quality of life (HRQoL) outcomes are important in making clinical and policy decisions. This study aimed to examine the HRQoL reporting in cancer drug trials leading to Food and...

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area

PurposeTo address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS.MethodsWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups.ResultsThis retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063).ConclusionsOur study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.