Lung cancer in syria: a retrospective study for clinical profiling and stage/smoking analysis

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While high-income countries have generated extensive epidemiological data, evidence from low- and middle-income nations—especially those affected by conflict—remains limited. We sought to describe the clinicopathological profile of lung cancer in Syria and to explore whether smoking history influences stage at diagnosis. Methods: We performed a retrospective review of all patients with histologically confirmed primary lung cancer seen at Al-Bayroni University Hospital, the Syrian national cancer center, from 2022 to 2024. Clinical variables included age, sex, smoking status, histological subtype, and TNM summary stage. Histologies were grouped into standard categories. Descriptive statistics were calculated, and associations between smoking and stage were evaluated using chi-square testing. Results: A total of 3,028 patients were identified. The mean age was 60.7 years (SD 15.5), and men predominated (84%). Most patients reported a smoking history (82%; 61% current, 21% former). Adenocarcinoma accounted for nearly half of cases (45.5%), followed by small cell carcinoma (21.6%) and squamous carcinoma (17.5%). Large cell (0.8%) and neuroendocrine tumors (1.0%) were rare, while other histologies comprised 13.6%. Late presentation was the rule: more than two-thirds were diagnosed at stage III or IV, with adenocarcinoma showing the highest proportion of stage IV disease (~ 77%). No meaningful association was found between smoking status and stage at diagnosis (p > 0.05 across subtypes). Conclusion: Lung cancer in Syria is marked by heavy male predominance, high smoking prevalence, a shift toward adenocarcinoma, and advanced presentation regardless of smoking. Strengthening diagnostic access and tobacco control should be priorities for reducing the national burden. Oncology Pulmonology Statistical Epidemiology lung Cancer Syria Clinical profile Descriptive Introduction Lung cancer remains the leading cause of cancer related mortality worldwide; it accounts for approximately one in every five cancer deaths which is clearly a persistent global health challenge that is addressed continuously [1]. Advancements have been made both in early detection and therapy. However, the prognosis for lung cancer remains poor, largely due to late-stage diagnosis[2]. While the overall incidence of lung cancer has plateaued or declined in many high-income countries due to preventive measures against well known risk factors such as tobacco smoking, low- and middle- income nations have witnessed a rising burden of lung cancer incidence, mirroring increased tobacco use, environmental exposure, and weak healthcare access[1]. In Syria, lung cancer contributes to a large slice of the most common malignancies among both men and women. Reflecting a compound of risk factors such as high rates of smoking, air pollution, low income, and more recently the profound impact of armed conflict on public health infrastructure. Despite the challenges, comprehensive data on the clinical profile of lung cancer in Syria remain scarce, and little is known about the distribution of histological subtypes pr the relationship between smoking status and stage at diagnosis[3]. The distribution of lung cancer histological subtypes is not constant across populations, with adenocarcinoma now surpassing squamous cell carcinoma as the most common subtype in many countries[4]. Small cell lung cancer is strongly linked to smoking, and continues to carry the worst prognosis mainly due to its aggressive biology and propensity for early metastasis[5]. Although smoking is considered the primary risk factor for most lung cancer types, a large proportion of patients -particularly women and adenocarcinoma patients- are never smokers. This highlights the complexity behind lung cancer etiology taking into account multiple factors other than smoking such as genetic, environmental, and occupational factors[4]. It is important to note that the correlation between smoking history and stage at diagnosis remains unclear in many low- and middle- income countries, where barriers to early detection still exist and access to care is often delayed[6]. Comprehensive, subtype-specific analyses from resource-limited settings are therefore essential to better understand the impact of smoking and to guide targeted prevention and early detection strategies. To address these gaps, we conducted a retrospective analysis of lung cancer cases diagnosed at Al Bayroni University Hospital, Syria’s largest and only national cancer center handling 60-70% of cancer patients in Syria [3]. Our aims were to delineate the demographic and clinicopathological features of lung cancer in a contemporary Syrian cohort, to characterize the distribution of major histological subtypes, and to evaluate the correlation between smoking history and stage at presentation. By providing detailed, site-specific data from a national referral center, this study seeks to inform future cancer control strategies in Syria and contribute to the global understanding of lung cancer epidemiology in conflict-affected regions. Methods We conducted a retrospective cohort study utilizing patient data from Al-Bayroni University Hospital, the primary national cancer center in Syria. All lung cancer cases diagnosed from January 2022 through December 2024 were identified and reviewed. Inclusion criteria consisted of adult patients aged between 18 and 100 years with histologically confirmed primary lung cancer. Exclusion criteria were patients with non-lung primaries, invalid or missing essential clinical data (age, gender, histological subtype, and smoking history), and age outliers (below 18 or above 100 years). The collected data included demographic information (age and gender), smoking history (categorized as current smoker, former smoker, or never smoked), histological subtypes (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, neuroendocrine carcinoma, and other rare types), and stage at diagnosis based on the TNM classification summarized into stages I through IV. Data were extracted from electronic medical records and pathology reports and then anonymized. Histological subtypes were categorized based on standard ICD-O-3 codes. Descriptive statistics were calculated, including means with standard deviations (SD) for continuous variables, and frequencies with percentages for categorical variables. Cross-tabulations and chi-square tests were performed to evaluate the correlation between smoking history and stage at diagnosis across the major histological subtypes. Statistical significance was defined at a p-value of <0.05. Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). Results The study cohort comprised 3,028 lung cancer patients diagnosed between 2022 and 2024. The mean age was 60.7 years (SD ± 15.5), with a marked male predominance (84.0% male, 16.0% female). The majority of patients were current smokers (61.1%), while former and never-smokers accounted for 21.0% and 17.9%, respectively. The most prevalent histological subtype was adenocarcinoma (45.5%), followed by small cell carcinoma (21.6%) and squamous cell carcinoma (17.5%). Large cell carcinoma and neuroendocrine carcinoma represented smaller proportions, at 0.8% and 1.0%, respectively, with other rare subtypes constituting the remaining 13.6%. For the smoking-stage correlation analysis (n = 1,989 patients with complete data), late-stage (III-IV) presentation predominated across all major histological subtypes and smoking statuses. Among 988 adenocarcinoma patients, stage IV was most common, particularly among never-smokers (83%) and current smokers (77%). Similarly, among 385 squamous cell carcinoma patients, stage IV represented approximately half of the cases across all smoking groups. In 417 small cell carcinoma patients, the majority (68–74%) presented at stage IV regardless of smoking status. Chi-square tests did not reveal statistically significant associations between smoking status and stage at diagnosis within any histological subtype (all p > 0.05). These findings highlight a significant proportion of advanced-stage lung cancer at diagnosis, irrespective of smoking history or histological subtype, reflecting challenges in early detection and emphasizing the urgent need for improved screening and awareness strategies in the Syrian population. Table 1 Clinical characteristics of lung cancer patients (2022–2024). Characteristic Value Total patients 3028 Age (years) 60.7 ± 15.5 (mean ± SD) Gender Male: 2543 (84.0%) Female: 485 (16.0%) Smoking history Current smoker: 1850 (61.1%) Former smoker: 635 (21.0%) Never smoked: 543 (17.9%) Histological subtype Adenocarcinoma: 1379 (45.5%) Squamous cell carcinoma: 530 (17.5%) Small cell carcinoma: 655 (21.6%) Large cell carcinoma: 23 (0.8%) Neuroendocrine carcinoma: 30 (1.0%) Other/rare: 411 (13.6%) Table 2 Stage at diagnosis by smoking status among patients with adenocarcinoma Stage Current Smoker, n (%) Former Smoker, n (%) Never Smoked, n (%) I 1 (0.1%) 2 (0.2%) 3 (0.3%) II 22 (2.2%) 9 (0.9%) 8 (0.8%) III 104 (10.5%) 41 (4.1%) 29 (2.9%) IV 431 (43.6%) 148 (15.0%) 190 (19.2%) Table 3 Stage at diagnosis by smoking status among patients with squamous cell carcinoma Stage Current Smoker, n (%) Former Smoker, n (%) Never Smoked, n (%) I 4 (1.0%) 1 (0.3%) 1 (0.3%) II 25 (6.5%) 13 (3.4%) 3 (0.8%) III 92 (23.9%) 21 (5.5%) 21 (5.5%) IV 136 (35.3%) 40 (10.4%) 28 (7.3%) Table 4 Stage at diagnosis by smoking status among patients with small cell carcinoma Stage Current Smoker, n (%) Former Smoker, n (%) Never Smoked, n (%) I 2 (0.5%) 1 (0.2%) 1 (0.2%) II 15 (3.6%) 6 (1.4%) 2 (0.5%) III 57 (13.7%) 21 (5.0%) 11 (2.6%) IV 212 (50.8%) 58 (13.9%) 31 (7.4%) Discussion This retrospective study provides a comprehensive analysis of the clinical and pathological profile of lung cancer in a large, contemporary cohort from Syria’s national cancer referral center. Our findings paint a stark picture of the lung cancer burden in a conflict-affected, middle-income nation, characterized by a striking male predominance, a high prevalence of smoking, a concerning shift towards adenocarcinoma, and an overwhelming trend toward late-stage diagnosis across all subtypes. Crucially, we found no significant association between smoking history and stage at diagnosis, suggesting that systemic barriers to healthcare access, rather than tumor biology linked to smoking, are the primary drivers of advanced disease presentation in this setting. Our analysis of 3,028 patients confirmed that lung cancer in Syria primarily affects male smokers, with a male-to-female ratio of 5:1 and over 82.1% of patients having a history of smoking. Adenocarcinoma was the most prevalent histological subtype (45.5%), followed by small cell carcinoma (21.6%) and squamous cell carcinoma (17.5%). The most alarming finding was the pervasive late-stage presentation: over two-thirds of all patients were diagnosed with stage IV disease, with adenocarcinoma exhibiting the highest rate (≈ 77%). A complete case analysis revealed no statistically significant correlation between smoking status (current, former, never) and stage at diagnosis for any of the major histological subtypes. The demographic profile of our cohort—predominantly male smokers with a mean age of 60.7 years—aligns with patterns seen in many regions with high tobacco use [1]. However, the extreme gender disparity (84.0% male) is notably higher than figures from Western countries and underscores the deeply entrenched smoking culture among Syrian men, likely exacerbated by psychosocial stressors linked to over a decade of conflict[2]. The ascendancy of adenocarcinoma as the leading subtype mirrors the global epidemiological shift [7]. This is a significant finding for Syria, as it suggests the influence of risk factors beyond traditional smoking, such as environmental pollution (e.g., from generators widespread due to destroyed infrastructure) or other unknown exposures, even within a predominantly smoking population. The high proportion of never-smokers within the adenocarcinoma subgroup (19.2%) further reinforces this point and is consistent with studies highlighting the distinct etiology of lung cancer in never-smokers [2]. The most critical finding is the overwhelming rate of advanced-stage diagnosis. This is consistent with previous reports from Syria and other LMICs highlighting resource-constrained healthcare systems [3,6]. The near-absence of stage I diagnoses (e.g., only ≈ 1% in adenocarcinoma) indicates a severe failure in early detection capabilities, likely due to a lack of screening programs, limited diagnostic facilities outside the capital, and patients delaying care due to financial hardship or prioritizing immediate survival needs during war[6]. The lack of association between smoking status and stage at diagnosis is a pivotal result. In high-income countries with robust healthcare systems, never-smokers might be diagnosed earlier due to a lower clinical suspicion for cancer, potentially delaying diagnosis. Our data suggests that in Syria, these biological or behavioral factors are completely overshadowed by overwhelming systemic barriers. Whether a patient is a heavy smoker or a never-smoker, they face the same immense obstacles to timely care—cost, travel, broken infrastructure, and lack of primary care referral—resulting in equally advanced disease by the time they reach the national center. This finding challenges the assumption that smoking-related aggressiveness is a primary driver of late stage and points directly to the healthcare system itself as the key variable. Implications of the Study Clinical and Public Health Implications: These results are an urgent call to action for Syrian health authorities and international aid organizations. Implementing low-dose CT screening programs, as seen in high-income countries, is currently unrealistic. Therefore, efforts must focus on achievable goals: (1) training primary care physicians on early symptoms of lung cancer to facilitate faster referral, (2) decentralizing diagnostic capabilities (e.g., enabling biopsies in major governorate hospitals), and (3) improving public awareness of persistent cough and other warning signs. The high rate of small cell carcinoma, a smoking-related and highly aggressive cancer, further emphasizes the critical need for robust tobacco control policies, which have likely been deprioritized during the conflict. Research Implications: This study provides an essential baseline for future research. The high rate of adenocarcinoma and never-smokers warrants investigation into environmental and genetic risk factors unique to the Syrian population. Furthermore, qualitative research into patient pathways to diagnosis is crucial to identify specific points of delay within the healthcare system that could be targeted with interventions. Limitations This study has several limitations inherent to its retrospective design and setting. Data was collected from a single center, albeit the national one handling most cases. The high rates of missing data for stage (e.g., 13–23% for main subtypes) and the need for complete-case analysis could introduce selection bias. “Former smoker” was not defined by a quit-time threshold, which may vary between individuals. Importantly, we could not account for critical variables like duration or intensity of smoking (pack-years), occupational exposures, socioeconomic status, or details on the diagnostic journey, all of which could provide deeper insight. Conclusion In conclusion, this study delineates a challenging landscape of lung cancer in Syria, defined by advanced-stage presentation irrespective of smoking history or histological subtype. The epidemiological shift toward adenocarcinoma signals a changing risk profile, while the universal delay in diagnosis underscores the devastating impact of prolonged conflict on healthcare access. Our findings confirm that the locus of control for improving lung cancer outcomes in Syria lies not primarily in novel therapeutics, but in strengthening foundational health systems, facilitating earlier diagnosis, and reigniting public health efforts against tobacco. Addressing these systemic barriers is the essential first step toward improving the prognosis for Syrian lung cancer patients. Declarations Ethics approval and consent to participate Ethical approval for this study was obtained from the Damascus University Faculty of Medicine Ethics Committee under the supervision of Prof. Radwan Al Ahmad. The study was conducted in accordance with the ethical standards of the institutional and national research committees. As this was a retrospective, non-interventional analysis of anonymized patient data, the Ethics Committee waived the requirement for individual informed consent. Consent for publication Not applicable. This study does not contain any identifiable individual data, images, or case material requiring consent for publication. Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Due to institutional policies and patient privacy considerations, raw data cannot be publicly shared. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions Zyad Al-Frejat: Conceptualization, Methodology, Data curation, Formal statistical analysis, Writing—original draft, and Corresponding author. Sami Masoud: Data collection, Validation, and Review of the manuscript. Fatima Al-Jojo: Data entry, Verification, and Assistance in literature review. Deema Al-Zoubi: Data organization, Quality control, and Editing of the manuscript. Prof. Radwan Al-Ahmad: Supervision, Methodological oversight, and Critical review of the final manuscript. Hazem Habib: Clinical interpretation, Visualization, and Review of results. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209–49. https://doi.org/10.3322/caac.21660. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74:12–49. https://doi.org/10.3322/CAAC.21820. Saifo M, Alali M, Alhabeb H, Awak M, Nahhat F, Manachi M. Lung Cancer in Syria. Journal of Thoracic Oncology 2024;19:534–40. https://doi.org/10.1016/j.jtho.2023.12.013. Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ. Lung cancer in never smokers - A review. Eur J Cancer 2012;48:1299–311. https://doi.org/10.1016/J.EJCA.2012.03.007/ASSET/E640F733-F18B-429E-B5CF-BBCDB6A84029/MAIN.ASSETS/GR1.JPG. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database. Journal of Clinical Oncology 2006;24:4539–44. https://doi.org/10.1200/JCO.2005.04.4859. Hanafi I, Abo Samra D, Alsaqqa R, Naeem A, Shebli B, Ajlyakin G. Lung Cancer Diagnoses and Outcomes during the Syrian War, 2011-2018. JAMA Netw Open 2024;7:E242091. https://doi.org/10.1001/JAMANETWORKOPEN.2024.2091,. Couraud S, Zalcman G, Milleron B, Morin F, Souquet P-J. Lung cancer in never smokers – A review. Eur J Cancer 2012;48:1299–311. https://doi.org/10.1016/j.ejca.2012.03.007. Additional Declarations The authors declare no competing interests. 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cancer remains the leading cause of cancer related mortality worldwide; it accounts for approximately one in every five cancer deaths which is clearly a persistent global health challenge that is addressed continuously [1]. Advancements have been made both in early detection and therapy. However, the prognosis for lung cancer remains poor, largely due to late-stage diagnosis[2]. While the overall incidence of lung cancer has plateaued or declined in many high-income countries due to preventive measures against well known risk factors such as tobacco smoking, low- and middle- income nations have witnessed a rising burden of lung cancer incidence, mirroring increased tobacco use, environmental exposure, and weak healthcare access[1].\u003c/p\u003e\n\u003cp\u003eIn Syria, lung cancer contributes to a large slice of the most common malignancies among both men and women. Reflecting a compound of risk factors such as high rates of smoking, air pollution, low income, and more recently the profound impact of armed conflict on public health infrastructure. Despite the challenges, comprehensive data on the clinical profile of lung cancer in Syria remain scarce, and little is known about the distribution of histological subtypes pr the relationship between smoking status and stage at diagnosis[3].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe distribution of lung cancer histological subtypes is not constant across populations, with adenocarcinoma now surpassing squamous cell carcinoma as the most common subtype in many countries[4]. Small cell lung cancer is strongly linked to smoking, and continues to carry the worst prognosis mainly due to its aggressive biology and propensity for early metastasis[5]. Although smoking is considered the primary risk factor for most lung cancer types, a large proportion of patients -particularly women and adenocarcinoma patients- are never smokers. This highlights the complexity behind lung cancer etiology taking into account multiple factors other than smoking such as genetic, environmental, and occupational factors[4]. It is important to note that the correlation between smoking history and stage at diagnosis remains unclear in many low- and middle- income countries, where barriers to early detection still exist and access to care is often delayed[6]. Comprehensive, subtype-specific analyses from resource-limited settings are therefore essential to better understand the impact of smoking and to guide targeted prevention and early detection strategies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo address these gaps, we conducted a retrospective analysis of lung cancer cases diagnosed at Al Bayroni University Hospital, Syria’s largest and only national cancer center handling 60-70% of cancer patients in Syria [3]. Our aims were to delineate the demographic and clinicopathological features of lung cancer in a contemporary Syrian cohort, to characterize the distribution of major histological subtypes, and to evaluate the correlation between smoking history and stage at presentation. By providing detailed, site-specific data from a national referral center, this study seeks to inform future cancer control strategies in Syria and contribute to the global understanding of lung cancer epidemiology in conflict-affected regions.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe conducted a retrospective cohort study utilizing patient data from Al-Bayroni University Hospital, the primary national cancer center in Syria. All lung cancer cases diagnosed from January 2022 through December 2024 were identified and reviewed. Inclusion criteria consisted of adult patients aged between 18 and 100 years with histologically confirmed primary lung cancer. Exclusion criteria were patients with non-lung primaries, invalid or missing essential clinical data (age, gender, histological subtype, and smoking history), and age outliers (below 18 or above 100 years).\u003c/p\u003e\n\u003cp\u003eThe collected data included demographic information (age and gender), smoking history (categorized as current smoker, former smoker, or never smoked), histological subtypes (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, neuroendocrine carcinoma, and other rare types), and stage at diagnosis based on the TNM classification summarized into stages I through IV. Data were extracted from electronic medical records and pathology reports and then anonymized. Histological subtypes were categorized based on standard ICD-O-3 codes.\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were calculated, including means with standard deviations (SD) for continuous variables, and frequencies with percentages for categorical variables. Cross-tabulations and chi-square tests were performed to evaluate the correlation between smoking history and stage at diagnosis across the major histological subtypes. Statistical significance was defined at a p-value of \u0026lt;0.05. Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study cohort comprised 3,028 lung cancer patients diagnosed between 2022 and 2024. The mean age was 60.7 years (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5), with a marked male predominance (84.0% male, 16.0% female). The majority of patients were current smokers (61.1%), while former and never-smokers accounted for 21.0% and 17.9%, respectively. The most prevalent histological subtype was adenocarcinoma (45.5%), followed by small cell carcinoma (21.6%) and squamous cell carcinoma (17.5%). Large cell carcinoma and neuroendocrine carcinoma represented smaller proportions, at 0.8% and 1.0%, respectively, with other rare subtypes constituting the remaining 13.6%.\u003c/p\u003e\u003cp\u003eFor the smoking-stage correlation analysis (n\u0026thinsp;=\u0026thinsp;1,989 patients with complete data), late-stage (III-IV) presentation predominated across all major histological subtypes and smoking statuses. Among 988 adenocarcinoma patients, stage IV was most common, particularly among never-smokers (83%) and current smokers (77%). Similarly, among 385 squamous cell carcinoma patients, stage IV represented approximately half of the cases across all smoking groups. In 417 small cell carcinoma patients, the majority (68\u0026ndash;74%) presented at stage IV regardless of smoking status. Chi-square tests did not reveal statistically significant associations between smoking status and stage at diagnosis within any histological subtype (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eThese findings highlight a significant proportion of advanced-stage lung cancer at diagnosis, irrespective of smoking history or histological subtype, reflecting challenges in early detection and emphasizing the urgent need for improved screening and awareness strategies in the Syrian population.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics of lung cancer patients (2022\u0026ndash;2024).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5 (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale: 2543 (84.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale: 485 (16.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent smoker: 1850 (61.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFormer smoker: 635 (21.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNever smoked: 543 (17.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistological subtype\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdenocarcinoma: 1379 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSquamous cell carcinoma: 530 (17.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSmall cell carcinoma: 655 (21.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLarge cell carcinoma: 23 (0.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeuroendocrine carcinoma: 30 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOther/rare: 411 (13.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eStage at diagnosis by smoking status among patients with adenocarcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFormer Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNever Smoked, n (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (0.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (0.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (2.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8 (0.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e104 (10.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41 (4.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29 (2.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e431 (43.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e148 (15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e190 (19.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eStage at diagnosis by smoking status among patients with squamous cell carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFormer Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNever Smoked, n (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (0.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (6.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (3.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (0.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e92 (23.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (5.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21 (5.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e136 (35.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40 (10.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e28 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eStage at diagnosis by smoking status among patients with small cell carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFormer Smoker, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNever Smoked, n (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (0.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (0.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15 (3.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (1.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (0.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57 (13.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (2.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e212 (50.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e58 (13.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e31 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study provides a comprehensive analysis of the clinical and pathological profile of lung cancer in a large, contemporary cohort from Syria\u0026rsquo;s national cancer referral center. Our findings paint a stark picture of the lung cancer burden in a conflict-affected, middle-income nation, characterized by a striking male predominance, a high prevalence of smoking, a concerning shift towards adenocarcinoma, and an overwhelming trend toward late-stage diagnosis across all subtypes. Crucially, we found no significant association between smoking history and stage at diagnosis, suggesting that systemic barriers to healthcare access, rather than tumor biology linked to smoking, are the primary drivers of advanced disease presentation in this setting.\u003c/p\u003e\u003cp\u003eOur analysis of 3,028 patients confirmed that lung cancer in Syria primarily affects male smokers, with a male-to-female ratio of 5:1 and over 82.1% of patients having a history of smoking. Adenocarcinoma was the most prevalent histological subtype (45.5%), followed by small cell carcinoma (21.6%) and squamous cell carcinoma (17.5%). The most alarming finding was the pervasive late-stage presentation: over two-thirds of all patients were diagnosed with stage IV disease, with adenocarcinoma exhibiting the highest rate (\u0026asymp;\u0026thinsp;77%). A complete case analysis revealed no statistically significant correlation between smoking status (current, former, never) and stage at diagnosis for any of the major histological subtypes.\u003c/p\u003e\u003cp\u003eThe demographic profile of our cohort\u0026mdash;predominantly male smokers with a mean age of 60.7 years\u0026mdash;aligns with patterns seen in many regions with high tobacco use [1]. However, the extreme gender disparity (84.0% male) is notably higher than figures from Western countries and underscores the deeply entrenched smoking culture among Syrian men, likely exacerbated by psychosocial stressors linked to over a decade of conflict[2].\u003c/p\u003e\u003cp\u003eThe ascendancy of adenocarcinoma as the leading subtype mirrors the global epidemiological shift [7]. This is a significant finding for Syria, as it suggests the influence of risk factors beyond traditional smoking, such as environmental pollution (e.g., from generators widespread due to destroyed infrastructure) or other unknown exposures, even within a predominantly smoking population. The high proportion of never-smokers within the adenocarcinoma subgroup (19.2%) further reinforces this point and is consistent with studies highlighting the distinct etiology of lung cancer in never-smokers [2].\u003c/p\u003e\u003cp\u003eThe most critical finding is the overwhelming rate of advanced-stage diagnosis. This is consistent with previous reports from Syria and other LMICs highlighting resource-constrained healthcare systems [3,6]. The near-absence of stage I diagnoses (e.g., only\u0026thinsp;\u0026asymp;\u0026thinsp;1% in adenocarcinoma) indicates a severe failure in early detection capabilities, likely due to a lack of screening programs, limited diagnostic facilities outside the capital, and patients delaying care due to financial hardship or prioritizing immediate survival needs during war[6].\u003c/p\u003e\u003cp\u003eThe lack of association between smoking status and stage at diagnosis is a pivotal result. In high-income countries with robust healthcare systems, never-smokers might be diagnosed earlier due to a lower clinical suspicion for cancer, potentially delaying diagnosis. Our data suggests that in Syria, these biological or behavioral factors are completely overshadowed by overwhelming systemic barriers. Whether a patient is a heavy smoker or a never-smoker, they face the same immense obstacles to timely care\u0026mdash;cost, travel, broken infrastructure, and lack of primary care referral\u0026mdash;resulting in equally advanced disease by the time they reach the national center. This finding challenges the assumption that smoking-related aggressiveness is a primary driver of late stage and points directly to the healthcare system itself as the key variable.\u003c/p\u003e\u003cp\u003eImplications of the Study\u003c/p\u003e\u003cp\u003eClinical and Public Health Implications: These results are an urgent call to action for Syrian health authorities and international aid organizations. Implementing low-dose CT screening programs, as seen in high-income countries, is currently unrealistic. Therefore, efforts must focus on achievable goals: (1) training primary care physicians on early symptoms of lung cancer to facilitate faster referral, (2) decentralizing diagnostic capabilities (e.g., enabling biopsies in major governorate hospitals), and (3) improving public awareness of persistent cough and other warning signs. The high rate of small cell carcinoma, a smoking-related and highly aggressive cancer, further emphasizes the critical need for robust tobacco control policies, which have likely been deprioritized during the conflict.\u003c/p\u003e\u003cp\u003eResearch Implications: This study provides an essential baseline for future research. The high rate of adenocarcinoma and never-smokers warrants investigation into environmental and genetic risk factors unique to the Syrian population. Furthermore, qualitative research into patient pathways to diagnosis is crucial to identify specific points of delay within the healthcare system that could be targeted with interventions.\u003c/p\u003e\u003cp\u003eLimitations\u003c/p\u003e\u003cp\u003eThis study has several limitations inherent to its retrospective design and setting. Data was collected from a single center, albeit the national one handling most cases. The high rates of missing data for stage (e.g., 13\u0026ndash;23% for main subtypes) and the need for complete-case analysis could introduce selection bias. \u0026ldquo;Former smoker\u0026rdquo; was not defined by a quit-time threshold, which may vary between individuals. Importantly, we could not account for critical variables like duration or intensity of smoking (pack-years), occupational exposures, socioeconomic status, or details on the diagnostic journey, all of which could provide deeper insight.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study delineates a challenging landscape of lung cancer in Syria, defined by advanced-stage presentation irrespective of smoking history or histological subtype. The epidemiological shift toward adenocarcinoma signals a changing risk profile, while the universal delay in diagnosis underscores the devastating impact of prolonged conflict on healthcare access. Our findings confirm that the locus of control for improving lung cancer outcomes in Syria lies not primarily in novel therapeutics, but in strengthening foundational health systems, facilitating earlier diagnosis, and reigniting public health efforts against tobacco. Addressing these systemic barriers is the essential first step toward improving the prognosis for Syrian lung cancer patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Damascus University Faculty of Medicine Ethics Committee under the supervision of Prof. Radwan Al Ahmad. The study was conducted in accordance with the ethical standards of the institutional and national research committees. As this was a retrospective, non-interventional analysis of anonymized patient data, the Ethics Committee waived the requirement for individual informed consent.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable. This study does not contain any identifiable individual data, images, or case material requiring consent for publication.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Due to institutional policies and patient privacy considerations, raw data cannot be publicly shared.\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\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eZyad Al-Frejat: Conceptualization, Methodology, Data curation, Formal statistical analysis, Writing—original draft, and Corresponding author.\u003cbr\u003e\u0026nbsp;Sami Masoud: Data collection, Validation, and Review of the manuscript.\u003cbr\u003e\u0026nbsp;Fatima Al-Jojo: Data entry, Verification, and Assistance in literature review.\u003cbr\u003e\u0026nbsp;Deema Al-Zoubi: Data organization, Quality control, and Editing of the manuscript.\u003cbr\u003e\u0026nbsp;Prof. Radwan Al-Ahmad: Supervision, Methodological oversight, and Critical review of the final manuscript.\u003c/p\u003e\n\u003cp\u003eHazem Habib: Clinical interpretation, Visualization, and Review of results.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":" References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209\u0026ndash;49. https://doi.org/10.3322/caac.21660.\u003c/li\u003e\n\u003cli\u003eSiegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74:12\u0026ndash;49. https://doi.org/10.3322/CAAC.21820.\u003c/li\u003e\n\u003cli\u003eSaifo M, Alali M, Alhabeb H, Awak M, Nahhat F, Manachi M. Lung Cancer in Syria. Journal of Thoracic Oncology 2024;19:534\u0026ndash;40. https://doi.org/10.1016/j.jtho.2023.12.013.\u003c/li\u003e\n\u003cli\u003eCouraud S, Zalcman G, Milleron B, Morin F, Souquet PJ. Lung cancer in never smokers - A review. Eur J Cancer 2012;48:1299\u0026ndash;311. https://doi.org/10.1016/J.EJCA.2012.03.007/ASSET/E640F733-F18B-429E-B5CF-BBCDB6A84029/MAIN.ASSETS/GR1.JPG.\u003c/li\u003e\n\u003cli\u003eGovindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database. Journal of Clinical Oncology 2006;24:4539\u0026ndash;44. https://doi.org/10.1200/JCO.2005.04.4859.\u003c/li\u003e\n\u003cli\u003eHanafi I, Abo Samra D, Alsaqqa R, Naeem A, Shebli B, Ajlyakin G. Lung Cancer Diagnoses and Outcomes during the Syrian War, 2011-2018. JAMA Netw Open 2024;7:E242091. https://doi.org/10.1001/JAMANETWORKOPEN.2024.2091,.\u003c/li\u003e\n\u003cli\u003eCouraud S, Zalcman G, Milleron B, Morin F, Souquet P-J. Lung cancer in never smokers \u0026ndash; A review. Eur J Cancer 2012;48:1299\u0026ndash;311. https://doi.org/10.1016/j.ejca.2012.03.007.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Damascus University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"lung Cancer, Syria, Clinical profile, Descriptive","lastPublishedDoi":"10.21203/rs.3.rs-7860786/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7860786/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eLung cancer is the leading cause of cancer mortality worldwide. While high-income countries have generated extensive epidemiological data, evidence from low- and middle-income nations\u0026mdash;especially those affected by conflict\u0026mdash;remains limited. We sought to describe the clinicopathological profile of lung cancer in Syria and to explore whether smoking history influences stage at diagnosis.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003e We performed a retrospective review of all patients with histologically confirmed primary lung cancer seen at Al-Bayroni University Hospital, the Syrian national cancer center, from 2022 to 2024. Clinical variables included age, sex, smoking status, histological subtype, and TNM summary stage. Histologies were grouped into standard categories. Descriptive statistics were calculated, and associations between smoking and stage were evaluated using chi-square testing.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eA total of 3,028 patients were identified. The mean age was 60.7 years (SD 15.5), and men predominated (84%). Most patients reported a smoking history (82%; 61% current, 21% former). Adenocarcinoma accounted for nearly half of cases (45.5%), followed by small cell carcinoma (21.6%) and squamous carcinoma (17.5%). Large cell (0.8%) and neuroendocrine tumors (1.0%) were rare, while other histologies comprised 13.6%. Late presentation was the rule: more than two-thirds were diagnosed at stage III or IV, with adenocarcinoma showing the highest proportion of stage IV disease (~\u0026thinsp;77%). No meaningful association was found between smoking status and stage at diagnosis (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 across subtypes).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eLung cancer in Syria is marked by heavy male predominance, high smoking prevalence, a shift toward adenocarcinoma, and advanced presentation regardless of smoking. Strengthening diagnostic access and tobacco control should be priorities for reducing the national burden.\u003c/p\u003e","manuscriptTitle":"Lung cancer in syria: a retrospective study for clinical profiling and stage/smoking analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-16 04:47:47","doi":"10.21203/rs.3.rs-7860786/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"df904634-91b0-4df0-bbfa-1a953fad717d","owner":[],"postedDate":"October 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56381313,"name":"Oncology"},{"id":56381314,"name":"Pulmonology"},{"id":56381315,"name":"Statistical Epidemiology"}],"tags":[],"updatedAt":"2025-10-16T04:47:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-16 04:47:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7860786","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7860786","identity":"rs-7860786","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}