Analysis of survival and prognostic factors in Lacrimal Gland Adenoid Cystic Carcinoma

Analysis of survival and prognostic factors in Lacrimal Gland Adenoid Cystic Carcinoma | 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 Analysis of survival and prognostic factors in Lacrimal Gland Adenoid Cystic Carcinoma Xinyun Wang, Huiling Ma, Ying Chen, Menghui Zhang, Sisi Liu, Xiawei Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9051039/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare, highly malignant tumor with poor prognosis. To identify prognostic factors associated with local recurrence, distant metastasis, and disease-specific survival (DSS), we conducted a retrospective study of 88 patients with LGACC. Methods A comprehensive LGACC dataset was constructed by integrating 7 cases treated at our institution with 81 additional cases identified through a systematic literature review. Associations between clinicopathologic variables and survival outcomes were evaluated using Kaplan–Meier survival analysis with log-rank testing, as well as univariate and multivariate Cox proportional hazards regression models. Results A total of 88 patients with LGACC were included. The age at diagnosis ranged from 9 to 86 years, with a slight male predominance. Median DSS was 60 months, median local-recurrence-free survival was 36 months, and median distant-metastasis-free survival was 49 months. The lung was the most frequent site of distant metastasis. Significant differences in DSS were observed across age groups, T categories, and surgical approaches ( P < 0.05). For local recurrence, survival curves differed significantly among T categories ( P < 0.05). With respect to distant metastasis, significant differences were identified between age groups, T categories, adjuvant chemotherapy groups, surgical approaches, and histopathologic subtypes ( P < 0.05). Conclusion T category is an independent prognostic factor for patient mortality, local recurrence, and distant metastasis in LGACC. Surgical approach independently influences DSS, while histopathologic subtype is an independent risk factor for distant metastasis. Biological sciences/Cancer Health sciences/Oncology Health sciences/Risk factors Lacrimal gland adenoid cystic carcinoma survival analysis prognostic factors case dataset Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare, aggressive secretory adenocarcinoma originating from the epithelial cells of the lacrimal gland, accounting for about 1.6% of all orbital tumors 1 – 6 . Between 2000 and 2021, the Surveillance, Epidemiology, and End Results (SEER) database in the United States recorded just over 100 cases of LGACC. Previous studies have reported a median age at diagnosis ranging from 38.9 to 41 years 3 , 5 , 7 . LGACC has been reported to occur more frequently in females, who account for 58%–70% of cases 3 – 5 . Typical presenting ocular symptoms of LGACC include unilateral proptosis, ptosis, and visual impairment. When perineural invasion occurs, patients may also experience periorbital pain and/or sensory disturbances 4 . Histopathologically, LGACC is classified into tubular, cribriform, and basaloid/solid subtypes, which commonly coexist in varying combinations within the same tumor. Due to its strong invasiveness and high rates of local recurrence, metastasis, and mortality 8 – 9 , the overall prognosis of LGACC remains poor, particularly for the basaloid/solid subtype 10 – 13 . Tumor staging and treatment modality further influence patient outcomes. Currently, treatment strategies for LGACC vary across different institutions and have not yet been standardized 3 , 6 , 11 , 14 – 20 . Surgical resection is generally considered the primary treatment modality for LGACC; however, the relative benefits of globe-preserving surgery or orbital exenteration for improving prognosis remain controversial 6 , 21 . LGACC frequently invades the bone wall, making complete surgical excision difficult to achieve 22 , 23 . Therefore, adjuvant radiotherapy, adjuvant chemotherapy, or other treatment modalities are often employed. The rarity of LGACC presents a significant challenge in formulating standardized treatment plans, predicting the recurrence risk of patients, and performing robust survival analyses. In this context, we sought to construct a comprehensive dataset of LGACC cases by combining retrospective clinical data from our institution with a systematic review of all published LGACC cases from 1967 to 2024. Using this aggregated dataset, we performed a detailed survival and prognostic analysis. Treatment strategies and survival outcomes were compared across tumor T categories according to the 8th Edition of the American Joint Committee on Cancer (AJCC) staging system. Potential prognostic factors influencing local recurrence, distant metastasis, and disease-specific mortality were explored. To our knowledge, this study represents the largest LGACC case series assembled to date, and the findings may provide more reliable evidence to inform clinical decision-making and prognostic assessment. METHODS This study included 7 patients with pathologically confirmed LGACC who were treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to January 2025. Clinical data were collected from electronic medical records and supplemented by telephone follow-up. Collected variables included age, sex, AJCC stage, surgical approach, adjuvant chemoradiotherapy, histopathologic subtype, presence of perineural invasion (PNI), duration of follow-up, survival status, local recurrence, and distant metastasis. These data are summarized in the supplementary materials (Supplementary material Table 1). All tumors were staged according to the 8th Edition of the AJCC staging system. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (Approval No.0073) .Informed consent was waived by the Institutional Review Board due to the retrospective nature of the study. We conducted a comprehensive literature review of the PubMed, Web of Science, and CNKI databases to identify all published reports of LGACC from 1967 to 2024. The search strategy included the terms “Adenoid cystic carcinoma” [Title/Abstract] AND “Lacrimal gland” [Title/Abstract]. Clinical data were extracted using the same variables as previously described. Studies were eligible for inclusion if they reported at least one prognostic outcome, including overall survival, local recurrence, or distant metastasis, and if the study design consisted of randomized controlled trials, retrospective or prospective cohort studies, case series, or case reports. Exclusion criteria included cases in which AJCC staging could not be determined according to the 8th Edition based on available information and studies in which patient prognosis was not reported. In total, 94 LGACC cases were identified, of which 13 were excluded. Ultimately, 81 published cases were included in the final analysis (Fig. 2 ). Detailed information is provided in the supplementary materials (Supplementary material Table 2). All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 26.0. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method, and differences between groups were assessed using the log-rank test, with a significance threshold set at α = 0.05. Prognostic factors were further evaluated using Cox regression analysis. To control for potential confounding factors, univariate Cox regression analyses were performed using a significance threshold of α = 0.1. Variables with P ≤ 0.1 in univariate analysis were subsequently entered into multivariate Cox regression models to identify independent prognostic factors, with statistical significance set at P < 0.05. Hazard ratios and corresponding 95% confidence intervals were calculated to quantify effect sizes. RESULTS Establishment of the LGACC Dataset A comprehensive dataset of patients with LGACC was established by integrating 7 cases treated at our institution with 81 cases identified from the published literature, yielding a total of 88 patients (Supplementary material Table 3). The age at diagnosis ranged from 9 to 86 years. The cohort included 45 male patients, 41 female patients, and 2 patients for whom sex was not reported. Median disease-specific survival (DSS) was 60 months, median local-recurrence-free survival (LRFS) was 36 months, and median distant-metastasis-free survival (DMFS) was 49 months. (Owing to the extensive temporal span of included literature cases and resultant heterogeneity in institutional follow-up protocols, a standardized 5-year follow-up endpoint was adopted.) 5-year Prognostic Survival Analysis Mortality Among the 88 patients with LGACC, 16 patients died within 5 years. Kaplan–Meier survival analysis demonstrated significant differences in survival curves among patients stratified by age group, T category and surgical approach ( P 40 years (HR = 3.129, 95%CI: 1.007–9.719, P = 0.0049), advanced T category (HR = 8.997, 95%CI: 3.060–26.452, P <0.001), and orbital exenteration (HR = 11.382, 95%CI: 4.014–32.272, P <0.001) were significantly associated with an increased risk of disease-specific mortality. Orbital exenteration was also associated with a markedly higher mortality risk than globe-preserving surgery. Multivariate Cox regression analysis identified T category and surgical approach as independent prognostic factors for disease-specific mortality (HR = 4.382, 95%CI: 1.179–16.291, P = 0.027). Local Recurrence Among the 88 patients with LGACC, 21 patients experienced local recurrence within 5 years. Kaplan–Meier analysis revealed significant differences in LRFS among patients stratified by T category ( P < 0.05; Fig. 4 ; Supplementary material Table 5). Univariate Cox regression analysis demonstrated that advanced T category (HR = 5.448, 95%CI: 2.198–13.504, P <0.001) was significantly associated with an increased risk of local recurrence. Multivariate Cox regression analysis confirmed T category as an independent prognostic factor for local recurrence (HR = 4.905, 95%CI: 1.945–12.368, P <0.001). Distant Metastasis Among the 88 patients with LGACC, 16 patients experienced distant metastasis within 5 years. Kaplan–Meier survival analysis demonstrated significant differences in DMFS among patients stratified by age group, T category, adjuvant chemotherapy status, surgical approach, and histopathologic subtype ( P < 0.05; Fig. 5 ; Supplementary material Table 6). Univariate Cox regression analysis indicated that advanced T category (HR = 12.205, 95%CI: 3.844–38.751, P <0.001), receipt of adjuvant chemotherapy (HR = 3.873, 95%CI: 1.333–11.247, P = 0.013), orbital exenteration (HR = 6.804, 95%CI: 2.391–19.368, P <0.001), and the predominantly basaloid/solid histopathologic subtype (HR = 4.428, 95%CI: 1.353–14.494, P = 0.014)were significantly associated with an increased risk of distant metastasis. Multivariate Cox regression analysis identified T category (HR = 7.376, 95%CI: 1.762–30.876, P = 0.006) and the predominantly basaloid/solid histopathologic subtype (HR = 4.745, 95%CI: 1.280–17.591, P = 0.020) as independent prognostic factors for distant metastasis. DISCUSSION Owing to the rarity of LGACC, most published studies investigating prognostic factors in LGACC are limited to small cohorts of 10–20 patients. To address this gap, we constructed a large LGACC case dataset by integrating 7 patients treated at our institution with 81 cases reported in the literature. Using this combined cohort, we systematically summarized the clinicopathologic characteristics of LGACC, identified prognostic risk factors through survival analyses, and evaluated treatment-related outcomes to provide clinically relevant insights. T category In our study, patients with T3–T4 stage had significantly higher risks of mortality, local recurrence, and distant metastasis than those with T1–T2 stage, indicating the central role of T category in prognosis. Ahmed et al. 3 also reported that patients with advanced LGACC tumors classified as T3–T4 according to the AJCC 6th edition experienced significantly higher mortality than those with early-stage disease. This observation was further corroborated by Yang et al. 24 using the AJCC 8th edition staging system. Importantly, Ahmed et al. 3 also demonstrated that among patients with T3–T4 stage, the absence of postoperative adjuvant radiotherapy was associated with an increased risk of local recurrence, underscoring the need for intensified treatment strategies in advanced-stage disease. Consistent with these findings, our survival analyses confirmed that T category is an independent risk factor for the prognosis of patients with LGACC. Histopathologic subtype Our study found that patients with the predominantly basaloid/solid histopathological subtype had a higher risk of distant metastasis. Several studies 4 , 5 have demonstrated that patients with predominantly basaloid/solid LGACC have a worse prognosis. Overall, these observations indicate that in patients with predominantly basaloid/solid histopathological subtype might require more aggressive systemic treatment to improve prognosis. Age Our survival analysis reported advanced age as an independent risk factor affecting the mortality and distant metastasis rates of patients with LGACC. Previous studies also found that younger patients with LGACC tend to have a better prognosis than adult patients, which may be attributed to the lower invasiveness of their tumors 1 . Bradley et al. 25 reported that age is a key determinant of mortality, with patients achieving better treatment outcomes being, on average, five years younger than those with poorer prognoses. Mallen et al. 26 identified age at diagnosis as an independent predictor of overall survival based on Kaplan–Meier analysis. Surgical approach Our survival analyses indicated that surgical approach was associated with patient prognosis, with orbital exenteration being linked to significantly higher mortality and distant metastasis rates. However, earlier studies reported that orbital exenteration did not confer a survival advantage in patients with LGACC 2 , 27 , 28 . This discrepancy may be explained by two factors: first, all patients in our hospital underwent globe-preserving surgery, which may introduce an analytical bias; second, the choice of surgical approach was inherently correlated with tumor stage, which directly affects prognosis. This suggests that tumor stage may confound the observed association between surgical approach and outcomes. Moreover, due to the functional impairment and facial disfigurement associated with this surgery, it usually decreases patients’ quality of life. Therefore, we propose implementing a multidisciplinary treatment model with preoperative chemoradiotherapy to reduce tumor volume, enabling complete resection while preserving the eye and thereby improving patients' postoperative quality of life. Adjuvant chemotherapy Our survival analysis showed that patients with LGACC who received adjuvant chemotherapy had significantly higher mortality and distant metastasis rates than those who did not receive chemotherapy, which is differ from some studies. Chemotherapeutic regimens for LGACC are largely extrapolated from those used for head and neck adenoid cystic carcinoma 29 , 30 . Platinum drugs such as cisplatin and anthracyclines like doxorubicin remains conventional chemotherapy for LGACC which have been demonstrated significant antitumor activity but are often limited by high toxicity 31 . To improve the prognosis of LGACC, neoadjuvant intra-arterial chemotherapy (NIAC) has been developed, which delivers high concentrations of chemotherapeutic drugs directly to tumor-feeding arteries, thereby reducing tumor burden and directly inhibiting the growth of tumor cells 15 , achieving more complete surgical resection. A study conducted in 2006 reported that NIAC increased the 5-year survival rate of patients with LGACC to 83.3% and reduced the 5-year cumulative recurrence rate to 23.8%, outperforming conventional chemotherapy 15 . Subsequent long-term follow-up over 18 years further confirmed significantly better prognostic outcomes with NIAC compared with conventional chemotherapy 32 .However, NIAC also has several potential risks including facial nerve palsy, swelling, vision loss, necrosis, and myelosuppression, etc 12 , 38 . In addition, due to the high costs and the demanding technical requirements, NIAC is currently limited to only a few specialized cancer centers and has not yet been incorporated into routine clinical treatment. This contradictory conclusion mainly attributed to the different chemotherapy methods. Among the 88 patients with LGACC in this study, only a few patients received NIAC, while the majority patients received conventional chemotherapy with poorer efficacy. The significant difference in treatment led to a reduction in the true therapeutic effect of NIAC in the chemotherapy groups. In the future, it is urgently necessary to expand the sample size to clarify its independent value. Limitations and prospects The rarity of LGACC has severely constrained the number of collected cases, thereby impeding in-depth research endeavors. Essential data, including T category and prognosis, are frequently absent or unattainable, which significantly complicates a comprehensive understanding of the disease. Moreover, accurately assessing prognosis and extending the follow-up time for patients is also essential in the future. In the present study, follow-up durations exhibited considerable variability, ranging from 6 months to more than a decade. The limited number of cases further complicated risk assessment. To accurately assess the clinical features, progression, and treatment outcomes of LGACC, the integration of global, multicenter data is imperative. By consolidating cases from diverse regions and medical centers, a comprehensive and heterogeneous database can be constructed, facilitating deeper insights and enhancing the reliability of prognostic predictions through larger sample analyses. Furthermore, Wang et al. 8 identified MYB–NFIB fusion as a key pathogenic alteration in LGACC. However, molecular research in this area remains constrained by the scarcity of cases, with the largest whole-exome sequencing study to date including only 14 LGACC cases 33 . Future work should focus on refining and augmenting gene sequencing protocols to determine the impact of specific molecular alterations on treatment outcomes and prognosis. CONCLUSION By establishing a comprehensive LGACC case database, this study demonstrated that those aged > 40 years, those with advanced-stage tumors (T3–T4), and those who underwent orbital exenteration exhibited significantly higher mortality rates. Advanced T category was also associated with increased local recurrence. Furthermore, advanced age, advanced T category, orbital exenteration, receipt of adjuvant chemotherapy, and predominantly basaloid/solid histopathologic subtype were associated with higher rates of distant metastasis. T category, surgical approach and histopathological subtype therefore provide important reference value for assessing disease severity, guiding treatment strategies, and predicting prognosis in patients with LGACC. Declarations Authors Affiliations Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China. Xinyun Wang Department of Ophthalmology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Huiling Ma & Ying Chen & Menghui Zhang & Sisi Liu & Xiawei Wang & Hongguang Cui Contributions Xinyun Wang concepted, drafted, and revised the manuscript. Huiling Ma drafted the manuscript. Ying Chen, Menghui Zhang, Sisi Liu, Xiawei Wang, and Hongguang Cui provided comments and revised the manuscript. All authors read and approved the final version of the manuscript. Funding This work was supported by the National Natural Science Foundation of China (Grant No. 82571251). Competing interests The authors declare that they have no competing interests. Consent for publication Waiver of informed consent. Ethics approval This study was approved by the Clinical Research Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine (the ethics approval ID: 2025B-0073). Data availability statement Figure 1 was created by the author to summarize the key findings of this study. All data relevant to the study are included in the article or uploaded as supplementary information. All the data included in our study are from published studies. Supplemental material The supplementary material, as provided by the authors, encompasses a cohort of patients with LGACC from the corresponding author's institution along with a systematic compilation of published literature on LGACC. References Tellado, M. V., McLean, I. W., Specht, C. S. & Varga, J. Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence. 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Investig. 123 , 2965–2968. 10.1172/jci67201 (2013). Tables Tables 1 to 6 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.docx supplementmaterial.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 06 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviewers invited by journal 24 Apr, 2026 Editor assigned by journal 24 Apr, 2026 Editor invited by journal 03 Apr, 2026 Submission checks completed at journal 01 Apr, 2026 First submitted to journal 01 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9051039","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":634408030,"identity":"0cb8aa0f-805d-4185-8d8b-e0d230570fff","order_by":0,"name":"Xinyun Wang","email":"","orcid":"","institution":"Lixiang Eye Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Xinyun","middleName":"","lastName":"Wang","suffix":""},{"id":634408034,"identity":"731610ca-e3b9-46f9-aab8-d15c38e80c51","order_by":1,"name":"Huiling Ma","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Huiling","middleName":"","lastName":"Ma","suffix":""},{"id":634408036,"identity":"9f5eb0d1-015a-4453-9368-b86b35fa4fcd","order_by":2,"name":"Ying Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Chen","suffix":""},{"id":634408038,"identity":"e691bfdb-910d-46be-9f1d-c84cc18ceb3f","order_by":3,"name":"Menghui Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Menghui","middleName":"","lastName":"Zhang","suffix":""},{"id":634408040,"identity":"9d0db479-26c5-456e-bfab-e62d09d358e9","order_by":4,"name":"Sisi Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sisi","middleName":"","lastName":"Liu","suffix":""},{"id":634408042,"identity":"399b09aa-4d24-487e-82d4-e317abdb0156","order_by":5,"name":"Xiawei Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiawei","middleName":"","lastName":"Wang","suffix":""},{"id":634408043,"identity":"55d65276-4437-4dfb-bc3c-6fbfed518f06","order_by":6,"name":"Hongguang Cui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACNvbmAwcSKmwYGBuAPB5itPDxHEt88OFMGgla5CRyjA1nth2G8IjSwsZzxkyah+28PfOMBMYHb9sY5M0JamFvK5Pm4bnNzDgjgdlwbhuD4c4GgrYc3ibNI3GbDaiFTZq3jSHB4AAhLRIJQIcZnOMBamH/TaSWFGPDGQkHJEC2MBOnBRzIB5INGHseNkvOOSdhuIGQFvl2YFQm/rOzN2xPPvjhTZmNPEFb4MCwARyZEsSqB1lHgtpRMApGwSgYYQAA8Ms9NNCjc78AAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hongguang","middleName":"","lastName":"Cui","suffix":""}],"badges":[],"createdAt":"2026-03-06 13:23:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9051039/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9051039/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108839009,"identity":"6f3bd593-8d90-43c6-980b-c70252dacd4c","added_by":"auto","created_at":"2026-05-09 00:40:16","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4540374,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival and prognostic factors of LGACC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSurvival analysis of 88 LGACC patients showed that T3-T4 stage was associated with a mortality risk 4.380 times, a local recurrence risk 4.905 times, and a distant metastasis risk 7.376 times higher than T1-T2. Orbital exenteration was linked to a mortality rate 11.315 times higher than globe-preserving surgery. Patients with predominantly basaloid/solid histology had a distant metastasis risk 4.745 times that of those with non-basaloid/solid subtypes.\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/3b6f5562ee2779de786fd14a.jpeg"},{"id":108838981,"identity":"c831175b-8929-4b32-9d58-f00e078acb53","added_by":"auto","created_at":"2026-05-09 00:40:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58921,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of the literature search and the process of inclusion and exclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 26.0. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method, and differences between groups were assessed using the log-rank test, with a significance threshold set at α =0.05. Prognostic factors were further evaluated using Cox regression analysis. To control for potential confounding factors, univariate Cox regression analyses were performed using a significance threshold of α=0.1. Variables with \u003cem\u003eP \u003c/em\u003e≤ 0.1 in univariate analysis were subsequently entered into multivariate Cox regression models to identify independent prognostic factors, with statistical significance set at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05. Hazard ratios and corresponding 95% confidence intervals were calculated to quantify effect sizes.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/a31334f599af2b736bc97317.png"},{"id":108838983,"identity":"36d7f015-b173-4ad4-ab40-9f910a1a2cfa","added_by":"auto","created_at":"2026-05-09 00:40:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":119246,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier analysis curves of mortality rates for the age group, T category group, and surgical approach group in the LGACC dataset\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLocal Recurrence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 88 patients with LGACC, 21 patients experienced local recurrence within 5 years. Kaplan–Meier analysis revealed significant differences in LRFS among patients stratified by T category (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05; Figure 4; Supplementary material Table 5).\u003c/p\u003e\n\u003cp\u003eUnivariate Cox regression analysis demonstrated that advanced T category (HR=5.448, 95%CI: 2.198–13.504, \u003cem\u003eP\u003c/em\u003e＜0.001) was significantly associated with an increased risk of local recurrence.\u003c/p\u003e\n\u003cp\u003eMultivariate Cox regression analysis confirmed T category as an independent prognostic factor for local recurrence (HR=4.905, 95%CI: 1.945–12.368, \u003cem\u003eP\u003c/em\u003e＜0.001).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/2b1406d886df06cd8daee622.png"},{"id":108838978,"identity":"501073b7-8ae2-4b72-90b7-02190dfb13d1","added_by":"auto","created_at":"2026-05-09 00:40:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":45374,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier analysis curve of the local recurrence rate for the T category group in the LGACC dataset\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/d7f1835a6b0b773d73095b64.png"},{"id":108838986,"identity":"4aa52655-fca8-43dd-9ff1-af73b9c3de5a","added_by":"auto","created_at":"2026-05-09 00:40:09","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":118640,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier analysis curves of distant metastasis rates for the age group, T category group, group with or without adjuvant chemotherapy, surgical approach group, and histopathologic subtype group in the LGACC dataset\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/8633a6a3559cbc317d8646e1.png"},{"id":108839014,"identity":"1a84573a-51b8-4fe3-8c70-731ce9160609","added_by":"auto","created_at":"2026-05-09 00:40:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5077638,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/53374282-1331-4ce0-a229-e95b1ef19aab.pdf"},{"id":108838982,"identity":"9dc3770f-4c52-43cb-b9ef-8c84b4ce7d17","added_by":"auto","created_at":"2026-05-09 00:40:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":189770,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/bdeaf85e2e9a00766a2e9d38.docx"},{"id":108838987,"identity":"3ab86d44-2d58-4111-8880-c1637c407faf","added_by":"auto","created_at":"2026-05-09 00:40:10","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":620144,"visible":true,"origin":"","legend":"","description":"","filename":"supplementmaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9051039/v1/f5a16a0e50d854719c1147a5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of survival and prognostic factors in Lacrimal Gland Adenoid Cystic Carcinoma","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eLacrimal gland adenoid cystic carcinoma (LGACC) is a rare, aggressive secretory adenocarcinoma originating from the epithelial cells of the lacrimal gland, accounting for about 1.6% of all orbital tumors\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Between 2000 and 2021, the Surveillance, Epidemiology, and End Results (SEER) database in the United States recorded just over 100 cases of LGACC. Previous studies have reported a median age at diagnosis ranging from 38.9 to 41 years \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. LGACC has been reported to occur more frequently in females, who account for 58%\u0026ndash;70% of cases\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Typical presenting ocular symptoms of LGACC include unilateral proptosis, ptosis, and visual impairment. When perineural invasion occurs, patients may also experience periorbital pain and/or sensory disturbances\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Histopathologically, LGACC is classified into tubular, cribriform, and basaloid/solid subtypes, which commonly coexist in varying combinations within the same tumor. Due to its strong invasiveness and high rates of local recurrence, metastasis, and mortality\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, the overall prognosis of LGACC remains poor, particularly for the basaloid/solid subtype\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Tumor staging and treatment modality further influence patient outcomes. Currently, treatment strategies for LGACC vary across different institutions and have not yet been standardized \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Surgical resection is generally considered the primary treatment modality for LGACC; however, the relative benefits of globe-preserving surgery or orbital exenteration for improving prognosis remain controversial\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. LGACC frequently invades the bone wall, making complete surgical excision difficult to achieve\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Therefore, adjuvant radiotherapy, adjuvant chemotherapy, or other treatment modalities are often employed. The rarity of LGACC presents a significant challenge in formulating standardized treatment plans, predicting the recurrence risk of patients, and performing robust survival analyses.\u003c/p\u003e \u003cp\u003eIn this context, we sought to construct a comprehensive dataset of LGACC cases by combining retrospective clinical data from our institution with a systematic review of all published LGACC cases from 1967 to 2024. Using this aggregated dataset, we performed a detailed survival and prognostic analysis. Treatment strategies and survival outcomes were compared across tumor T categories according to the 8th Edition of the American Joint Committee on Cancer (AJCC) staging system. Potential prognostic factors influencing local recurrence, distant metastasis, and disease-specific mortality were explored. To our knowledge, this study represents the largest LGACC case series assembled to date, and the findings may provide more reliable evidence to inform clinical decision-making and prognostic assessment.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis study included 7 patients with pathologically confirmed LGACC who were treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to January 2025. Clinical data were collected from electronic medical records and supplemented by telephone follow-up. Collected variables included age, sex, AJCC stage, surgical approach, adjuvant chemoradiotherapy, histopathologic subtype, presence of perineural invasion (PNI), duration of follow-up, survival status, local recurrence, and distant metastasis. These data are summarized in the supplementary materials (Supplementary material Table\u0026nbsp;1). All tumors were staged according to the 8th Edition of the AJCC staging system. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (Approval No.0073) .Informed consent was waived by the Institutional Review Board due to the retrospective nature of the study.\u003c/p\u003e \u003cp\u003eWe conducted a comprehensive literature review of the PubMed, Web of Science, and CNKI databases to identify all published reports of LGACC from 1967 to 2024. The search strategy included the terms \u0026ldquo;Adenoid cystic carcinoma\u0026rdquo; [Title/Abstract] AND \u0026ldquo;Lacrimal gland\u0026rdquo; [Title/Abstract]. Clinical data were extracted using the same variables as previously described. Studies were eligible for inclusion if they reported at least one prognostic outcome, including overall survival, local recurrence, or distant metastasis, and if the study design consisted of randomized controlled trials, retrospective or prospective cohort studies, case series, or case reports. Exclusion criteria included cases in which AJCC staging could not be determined according to the 8th Edition based on available information and studies in which patient prognosis was not reported. In total, 94 LGACC cases were identified, of which 13 were excluded. Ultimately, 81 published cases were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Detailed information is provided in the supplementary materials (Supplementary material Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAll statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 26.0. Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Survival outcomes were estimated using the Kaplan\u0026ndash;Meier method, and differences between groups were assessed using the log-rank test, with a significance threshold set at α\u0026thinsp;=\u0026thinsp;0.05. Prognostic factors were further evaluated using Cox regression analysis. To control for potential confounding factors, univariate Cox regression analyses were performed using a significance threshold of α\u0026thinsp;=\u0026thinsp;0.1. Variables with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.1 in univariate analysis were subsequently entered into multivariate Cox regression models to identify independent prognostic factors, with statistical significance set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Hazard ratios and corresponding 95% confidence intervals were calculated to quantify effect sizes.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEstablishment of the LGACC Dataset\u003c/h2\u003e \u003cp\u003eA comprehensive dataset of patients with LGACC was established by integrating 7 cases treated at our institution with 81 cases identified from the published literature, yielding a total of 88 patients (Supplementary material Table\u0026nbsp;3). The age at diagnosis ranged from 9 to 86 years. The cohort included 45 male patients, 41 female patients, and 2 patients for whom sex was not reported. Median disease-specific survival (DSS) was 60 months, median local-recurrence-free survival (LRFS) was 36 months, and median distant-metastasis-free survival (DMFS) was 49 months. (Owing to the extensive temporal span of included literature cases and resultant heterogeneity in institutional follow-up protocols, a standardized 5-year follow-up endpoint was adopted.)\u003c/p\u003e \u003cp\u003e \u003cb\u003e5-year Prognostic Survival Analysis\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMortality\u003c/h3\u003e\n\u003cp\u003eAmong the 88 patients with LGACC, 16 patients died within 5 years. Kaplan\u0026ndash;Meier survival analysis demonstrated significant differences in survival curves among patients stratified by age group, T category and surgical approach (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; Supplementary material Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003eUnivariate Cox regression analysis showed that age\u0026thinsp;\u0026gt;\u0026thinsp;40 years (HR\u0026thinsp;=\u0026thinsp;3.129, 95%CI: 1.007\u0026ndash;9.719, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0049), advanced T category (HR\u0026thinsp;=\u0026thinsp;8.997, 95%CI: 3.060\u0026ndash;26.452, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), and orbital exenteration (HR\u0026thinsp;=\u0026thinsp;11.382, 95%CI: 4.014\u0026ndash;32.272, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) were significantly associated with an increased risk of disease-specific mortality. Orbital exenteration was also associated with a markedly higher mortality risk than globe-preserving surgery.\u003c/p\u003e \u003cp\u003eMultivariate Cox regression analysis identified T category and surgical approach as independent prognostic factors for disease-specific mortality (HR\u0026thinsp;=\u0026thinsp;4.382, 95%CI: 1.179\u0026ndash;16.291, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eLocal Recurrence\u003c/h3\u003e\n\u003cp\u003eAmong the 88 patients with LGACC, 21 patients experienced local recurrence within 5 years. Kaplan\u0026ndash;Meier analysis revealed significant differences in LRFS among patients stratified by T category (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e; Supplementary material Table\u0026nbsp;5).\u003c/p\u003e \u003cp\u003eUnivariate Cox regression analysis demonstrated that advanced T category (HR\u0026thinsp;=\u0026thinsp;5.448, 95%CI: 2.198\u0026ndash;13.504, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) was significantly associated with an increased risk of local recurrence.\u003c/p\u003e \u003cp\u003eMultivariate Cox regression analysis confirmed T category as an independent prognostic factor for local recurrence (HR\u0026thinsp;=\u0026thinsp;4.905, 95%CI: 1.945\u0026ndash;12.368, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eDistant Metastasis\u003c/h3\u003e\n\u003cp\u003eAmong the 88 patients with LGACC, 16 patients experienced distant metastasis within 5 years. Kaplan\u0026ndash;Meier survival analysis demonstrated significant differences in DMFS among patients stratified by age group, T category, adjuvant chemotherapy status, surgical approach, and histopathologic subtype (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e; Supplementary material Table\u0026nbsp;6).\u003c/p\u003e \u003cp\u003eUnivariate Cox regression analysis indicated that advanced T category (HR\u0026thinsp;=\u0026thinsp;12.205, 95%CI: 3.844\u0026ndash;38.751, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), receipt of adjuvant chemotherapy (HR\u0026thinsp;=\u0026thinsp;3.873, 95%CI: 1.333\u0026ndash;11.247, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), orbital exenteration (HR\u0026thinsp;=\u0026thinsp;6.804, 95%CI: 2.391\u0026ndash;19.368, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), and the predominantly basaloid/solid histopathologic subtype (HR\u0026thinsp;=\u0026thinsp;4.428, 95%CI: 1.353\u0026ndash;14.494, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014)were significantly associated with an increased risk of distant metastasis.\u003c/p\u003e \u003cp\u003eMultivariate Cox regression analysis identified T category (HR\u0026thinsp;=\u0026thinsp;7.376, 95%CI: 1.762\u0026ndash;30.876, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) and the predominantly basaloid/solid histopathologic subtype (HR\u0026thinsp;=\u0026thinsp;4.745, 95%CI: 1.280\u0026ndash;17.591, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020) as independent prognostic factors for distant metastasis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOwing to the rarity of LGACC, most published studies investigating prognostic factors in LGACC are limited to small cohorts of 10\u0026ndash;20 patients. To address this gap, we constructed a large LGACC case dataset by integrating 7 patients treated at our institution with 81 cases reported in the literature. Using this combined cohort, we systematically summarized the clinicopathologic characteristics of LGACC, identified prognostic risk factors through survival analyses, and evaluated treatment-related outcomes to provide clinically relevant insights.\u003c/p\u003e\n\u003ch3\u003eT category\u003c/h3\u003e\n\u003cp\u003eIn our study, patients with T3\u0026ndash;T4 stage had significantly higher risks of mortality, local recurrence, and distant metastasis than those with T1\u0026ndash;T2 stage, indicating the central role of T category in prognosis. Ahmed et al.\u003csup\u003e3\u003c/sup\u003e also reported that patients with advanced LGACC tumors classified as T3\u0026ndash;T4 according to the AJCC 6th edition experienced significantly higher mortality than those with early-stage disease. This observation was further corroborated by Yang et al.\u003csup\u003e24\u003c/sup\u003e using the AJCC 8th edition staging system. Importantly, Ahmed et al.\u003csup\u003e3\u003c/sup\u003e also demonstrated that among patients with T3\u0026ndash;T4 stage, the absence of postoperative adjuvant radiotherapy was associated with an increased risk of local recurrence, underscoring the need for intensified treatment strategies in advanced-stage disease. Consistent with these findings, our survival analyses confirmed that T category is an independent risk factor for the prognosis of patients with LGACC.\u003c/p\u003e\n\u003ch3\u003eHistopathologic subtype\u003c/h3\u003e\n\u003cp\u003eOur study found that patients with the predominantly basaloid/solid histopathological subtype had a higher risk of distant metastasis. Several studies\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e have demonstrated that patients with predominantly basaloid/solid LGACC have a worse prognosis. Overall, these observations indicate that in patients with predominantly basaloid/solid histopathological subtype might require more aggressive systemic treatment to improve prognosis.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAge\u003c/h2\u003e \u003cp\u003eOur survival analysis reported advanced age as an independent risk factor affecting the mortality and distant metastasis rates of patients with LGACC. Previous studies also found that younger patients with LGACC tend to have a better prognosis than adult patients, which may be attributed to the lower invasiveness of their tumors\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Bradley et al.\u003csup\u003e25\u003c/sup\u003e reported that age is a key determinant of mortality, with patients achieving better treatment outcomes being, on average, five years younger than those with poorer prognoses. Mallen et al.\u003csup\u003e26\u003c/sup\u003e identified age at diagnosis as an independent predictor of overall survival based on Kaplan\u0026ndash;Meier analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSurgical approach\u003c/h2\u003e \u003cp\u003eOur survival analyses indicated that surgical approach was associated with patient prognosis, with orbital exenteration being linked to significantly higher mortality and distant metastasis rates. However, earlier studies reported that orbital exenteration did not confer a survival advantage in patients with LGACC \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. This discrepancy may be explained by two factors: first, all patients in our hospital underwent globe-preserving surgery, which may introduce an analytical bias; second, the choice of surgical approach was inherently correlated with tumor stage, which directly affects prognosis. This suggests that tumor stage may confound the observed association between surgical approach and outcomes.\u003c/p\u003e \u003cp\u003eMoreover, due to the functional impairment and facial disfigurement associated with this surgery, it usually decreases patients\u0026rsquo; quality of life. Therefore, we propose implementing a multidisciplinary treatment model with preoperative chemoradiotherapy to reduce tumor volume, enabling complete resection while preserving the eye and thereby improving patients' postoperative quality of life.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAdjuvant chemotherapy\u003c/h2\u003e \u003cp\u003eOur survival analysis showed that patients with LGACC who received adjuvant chemotherapy had significantly higher mortality and distant metastasis rates than those who did not receive chemotherapy, which is differ from some studies.\u003c/p\u003e \u003cp\u003eChemotherapeutic regimens for LGACC are largely extrapolated from those used for head and neck adenoid cystic carcinoma\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Platinum drugs such as cisplatin and anthracyclines like doxorubicin remains conventional chemotherapy for LGACC which have been demonstrated significant antitumor activity but are often limited by high toxicity\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. To improve the prognosis of LGACC, neoadjuvant intra-arterial chemotherapy (NIAC) has been developed, which delivers high concentrations of chemotherapeutic drugs directly to tumor-feeding arteries, thereby reducing tumor burden and directly inhibiting the growth of tumor cells\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, achieving more complete surgical resection. A study conducted in 2006 reported that NIAC increased the 5-year survival rate of patients with LGACC to 83.3% and reduced the 5-year cumulative recurrence rate to 23.8%, outperforming conventional chemotherapy\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Subsequent long-term follow-up over 18 years further confirmed significantly better prognostic outcomes with NIAC compared with conventional chemotherapy\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.However, NIAC also has several potential risks including facial nerve palsy, swelling, vision loss, necrosis, and myelosuppression, etc \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, 38\u003c/sup\u003e. In addition, due to the high costs and the demanding technical requirements, NIAC is currently limited to only a few specialized cancer centers and has not yet been incorporated into routine clinical treatment.\u003c/p\u003e \u003cp\u003eThis contradictory conclusion mainly attributed to the different chemotherapy methods. Among the 88 patients with LGACC in this study, only a few patients received NIAC, while the majority patients received conventional chemotherapy with poorer efficacy. The significant difference in treatment led to a reduction in the true therapeutic effect of NIAC in the chemotherapy groups. In the future, it is urgently necessary to expand the sample size to clarify its independent value.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and prospects\u003c/h2\u003e \u003cp\u003eThe rarity of LGACC has severely constrained the number of collected cases, thereby impeding in-depth research endeavors. Essential data, including T category and prognosis, are frequently absent or unattainable, which significantly complicates a comprehensive understanding of the disease. Moreover, accurately assessing prognosis and extending the follow-up time for patients is also essential in the future. In the present study, follow-up durations exhibited considerable variability, ranging from 6 months to more than a decade. The limited number of cases further complicated risk assessment. To accurately assess the clinical features, progression, and treatment outcomes of LGACC, the integration of global, multicenter data is imperative. By consolidating cases from diverse regions and medical centers, a comprehensive and heterogeneous database can be constructed, facilitating deeper insights and enhancing the reliability of prognostic predictions through larger sample analyses.\u003c/p\u003e \u003cp\u003eFurthermore, Wang et al. \u003csup\u003e8\u003c/sup\u003e identified MYB\u0026ndash;NFIB fusion as a key pathogenic alteration in LGACC. However, molecular research in this area remains constrained by the scarcity of cases, with the largest whole-exome sequencing study to date including only 14 LGACC cases\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Future work should focus on refining and augmenting gene sequencing protocols to determine the impact of specific molecular alterations on treatment outcomes and prognosis.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eBy establishing a comprehensive LGACC case database, this study demonstrated that those aged\u0026thinsp;\u0026gt;\u0026thinsp;40 years, those with advanced-stage tumors (T3\u0026ndash;T4), and those who underwent orbital exenteration exhibited significantly higher mortality rates. Advanced T category was also associated with increased local recurrence. Furthermore, advanced age, advanced T category, orbital exenteration, receipt of adjuvant chemotherapy, and predominantly basaloid/solid histopathologic subtype were associated with higher rates of distant metastasis. T category, surgical approach and histopathological subtype therefore provide important reference value for assessing disease severity, guiding treatment strategies, and predicting prognosis in patients with LGACC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthors Affiliations\u003c/p\u003e\n\u003cp\u003eDepartment of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China.\u003c/p\u003e\n\u003cp\u003eXinyun\u0026nbsp;Wang\u003c/p\u003e\n\u003cp\u003eDepartment of Ophthalmology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.\u003c/p\u003e\n\u003cp\u003eHuiling Ma \u0026amp; Ying Chen \u0026amp; Menghui Zhang \u0026amp; Sisi Liu \u0026amp; Xiawei Wang \u0026amp; Hongguang Cui\u003c/p\u003e\n\u003cp\u003eContributions\u003c/p\u003e\n\u003cp\u003eXinyun Wang concepted, drafted, and revised the manuscript. Huiling Ma drafted the manuscript. Ying Chen, Menghui Zhang, Sisi Liu, Xiawei Wang, and Hongguang Cui provided comments and revised the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (Grant No. 82571251).\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWaiver of informed consent.\u003c/p\u003e\n\u003cp\u003eEthics approval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Clinical Research Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine (the ethics approval ID: 2025B-0073).\u003c/p\u003e\n\u003cp\u003eData availability statement\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure 1 was created by the author to summarize the key findings of this study. All data relevant to the study are included in the article or uploaded as supplementary information. All the data included in our study are from published studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSupplemental material\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe supplementary material, as provided by the authors, encompasses a cohort of patients with LGACC from the corresponding author\u0026apos;s institution along with a systematic compilation of published literature on LGACC.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTellado, M. V., McLean, I. W., Specht, C. S. \u0026amp; Varga, J. 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Investig.\u003c/em\u003e \u003cb\u003e123\u003c/b\u003e, 2965\u0026ndash;2968. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/jci67201\u003c/span\u003e\u003cspan address=\"10.1172/jci67201\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2013).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"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":"Lacrimal gland adenoid cystic carcinoma, survival analysis, prognostic factors, case dataset","lastPublishedDoi":"10.21203/rs.3.rs-9051039/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9051039/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLacrimal gland adenoid cystic carcinoma (LGACC) is a rare, highly malignant tumor with poor prognosis. To identify prognostic factors associated with local recurrence, distant metastasis, and disease-specific survival (DSS), we conducted a retrospective study of 88 patients with LGACC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e A comprehensive LGACC dataset was constructed by integrating 7 cases treated at our institution with 81 additional cases identified through a systematic literature review. Associations between clinicopathologic variables and survival outcomes were evaluated using Kaplan\u0026ndash;Meier survival analysis with log-rank testing, as well as univariate and multivariate Cox proportional hazards regression models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 88 patients with LGACC were included. The age at diagnosis ranged from 9 to 86 years, with a slight male predominance. Median DSS was 60 months, median local-recurrence-free survival was 36 months, and median distant-metastasis-free survival was 49 months. The lung was the most frequent site of distant metastasis. Significant differences in DSS were observed across age groups, T categories, and surgical approaches (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For local recurrence, survival curves differed significantly among T categories (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). With respect to distant metastasis, significant differences were identified between age groups, T categories, adjuvant chemotherapy groups, surgical approaches, and histopathologic subtypes (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eT category is an independent prognostic factor for patient mortality, local recurrence, and distant metastasis in LGACC. Surgical approach independently influences DSS, while histopathologic subtype is an independent risk factor for distant metastasis.\u003c/p\u003e","manuscriptTitle":"Analysis of survival and prognostic factors in Lacrimal Gland Adenoid Cystic Carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-09 00:39:14","doi":"10.21203/rs.3.rs-9051039/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-06T07:45:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254213162864480357621249472590762191734","date":"2026-05-04T22:24:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-24T14:59:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-24T14:51:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-03T23:42:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-01T15:35:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-04-01T13:03:23+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":"a67b8ada-c925-46e4-9393-e103a2042d65","owner":[],"postedDate":"May 9th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-06T07:45:32+00:00","index":79,"fulltext":""},{"type":"reviewerAgreed","content":"254213162864480357621249472590762191734","date":"2026-05-04T22:24:34+00:00","index":78,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":67515521,"name":"Biological sciences/Cancer"},{"id":67515522,"name":"Health sciences/Oncology"},{"id":67515523,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-05-09T00:39:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-09 00:39:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9051039","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9051039","identity":"rs-9051039","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}