The Impact of Some Clinicopathological Factors on the Overall Survival in Metastatic Lung Cancer

The Impact of Some Clinicopathological Factors on the Overall Survival in Metastatic Lung Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Impact of Some Clinicopathological Factors on the Overall Survival in Metastatic Lung Cancer Alya Al Zobair, Rami Al Hayali, Ahmed Ali Albakr This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9033388/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The survival of patients with distinct metastatic locations varies due to the disparities in biological heterogeneity and treatment techniques. This study aims to assess how distant organ metastases, clinical characteristics, and pathological variables affect lung cancer patients' overall survival. Method: This is a prospective survival study conducted on 100 patients with metastatic lung cancer. Metastatic sites were either intrathoracic metastases, including patients with separate tumor nodules in a contralateral lobe, pleural nodules, pleural effusion, or pericardial effusion, or extrathoracic metastases involving the liver, bone, brain, adrenal gland, or other organ. All patients were monitored regularly every 1–3 months for a minimum of 20 months. For each patient, the date of death or the last follow-up visit since diagnosis was recorded. Result: Intrathoracic metastasis and the brain were the most frequent sites of metastases, followed by the liver and bone. Patients with multiorgan metastases had significantly shorter overall survival compared with those patients with single organ metastasis. Patients with lung cancer and intrathoracic metastases have the best survival rates, while those with liver metastases have the poorest outcomes . Conclusion: . It is crucial to consider this variation in survival on metastatic sites to ensure a more tailored and effective approach when developing treatment plans for metastatic lung cancer. Biological sciences/Cancer Health sciences/Medical research Health sciences/Oncology Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Breast and lung cancers are the most prevalent cancers worldwide; however, lung cancer remains the leading cause of cancer-related mortality globally ( 1 , 2 ) . Unfortunately, more than half of lung cancer patients are diagnosed at an advanced stage due to the lack of screening programs in most developed and developing nations ( 3 ) . The estimated overall survival following the diagnosis of metastasis was less than 12 months until a few years ago, and it is usually associated with a poor quality of life and high burden of symptoms ( 1 , 4 , 5 ) . Advancements in cancer treatment, including immunotherapy and molecular targeted therapy, offer substitutes for the standard forms of radiation and chemotherapy; however, metastatic lung cancer is still an incurable condition ( 6 , 7 ), and only 4.9% of people survive for five years ( 8 ) . The most frequent metastatic sites in patients with advanced lung cancer at the time of diagnosis or during follow-up are the liver, bone, adrenal, and central nervous system ( 8 ) . The World Health Organization (WHO) lists squamous cell carcinoma, adenocarcinoma, small-cell carcinoma, and large-cell carcinoma as the most frequent primary histological types of lung cancer. The biological characteristics and prognosis of these histological types vary, with small-cell lung cancer (SCLC) frequently being contrasted with the three remaining non-small-cell lung cancers (NSCLCs) ( 8 ) . Genetic testing plays a crucial role in precisely identifying lung cancer subtypes, enabling more targeted and effective treatment strategies that enhance therapeutic outcomes ( 9 ) . Sex, histological subtype, and age at diagnosis may affect the metastatic locations and survival in metastatic lung cancer ( 10 ) . Due to the disparities in biological differences and treatment techniques, the survival of patients with distinct metastatic locations varies. For this reason, understanding the metastatic patterns is essential to adjusting the therapy and monitoring plans, hence, this study aims to assess how distant organ metastases, clinical characteristics, and pathological variables affect lung cancer patients' overall survival. Patients and methods This is a prospective survival study conducted on patients with metastatic lung cancer who were diagnosed in the period between first Jan, 2020 and first Jan, 2022 and received treatment at Mosul Oncology Hospital in Iraq. Pathological specimens were analyzed to confirm lung cancer diagnoses in all patients, and the classification of pathological diagnoses was conducted according to the WHO classification ( 11 ) . The study was approved by the Scientific Committee of the College of Medicine, University of Mosul, and conducted in accordance with the Helsinki Declaration, written informed consent was obtained from all participants before their enrollment in the study. Inclusion criteria included the following: Patients diagnosed with stage IV (metastatic) primary lung cancer Having histological types limited to adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell carcinoma Lung cancer is the only primary tumor. Exclusion criteria: Patients with incomplete data. Patients who were lost to follow-up. Histopathological diagnosis other than the above-mentioned types. All the patients had a staging workup that included a computed tomography (CT) scan of the chest, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the brain. Bone scintigraphy as well as positron emission tomography/computed tomography (PET/CT) scan were done for selected cases. The eighth edition of the American Joint Committee on Cancer (AJCC) staging manual was used to stage the patients. Treatment was given according to the National Comprehensive Cancer Network (NCCN) guidelines ( 12 , 13 ) . Patients' clinicopathological characteristics were documented, including age, performance status (PS) at diagnosis (ECOG scoring system), comorbidities, sites of metastasis, histological type, and molecular subtypes. ( 14 ) The patients were identified as having a single or multiple metastases. Metastatic sites were either intrathoracic metastases, including patients with separate tumor nodules in a contralateral lobe, pleural nodules, pleural effusion, or pericardial effusion, or extrathoracic metastases involving the liver, bone, brain, adrenal gland, or other organ All patients were monitored regularly every 1–3 months for a minimum of 20 months. For each patient, the date of death or the last follow-up visit since diagnosis was recorded. Statistical analysis and data management were done using Version 20, SPSS. Survival analysis was used to estimate the impact of the site of metastasis and other clinical and pathological factors on the patient's survival. Results One hundred patients with metastatic lung cancer were included in this study. Their mean age was 63.7 years, ranging from 45–81 years, of whom 65% were male and 35% were female. The mean age of the included male patients was 65 years, ranging from 53 to 81 years, while the mean age of the included female patients was 60 years, ranging from 45 to 77 years. Seventy-five percent of the male patients were current or x-smokers, a significantly higher proportion compared to 45% of female patients. At the time of metastatic lung cancer diagnosis, 46% of patients had comorbidities, including hypertension, diabetes mellitus, ischemic heart disease, and others, with hypertension being the most common. The majority of patients (55%) had a good performance status at diagnosis (ECOG PS 0–1). NSCLC represented 85% of cases, and adenocarcinoma was the most frequent histopathological subtype of lung cancer, as shown in Table 1 . Table 1 Clinical, demographic and histopathological characteristics of the included patients with metastatic lung cancer. Characteristics Number Gender Male 65 Female 35 Smoking Never smoked 35 Current or former smoker 65 ECOG PS 0–1 55 2–3 45 Comorbidities Present 46 Absent 54 Histology Adenocarcinoma 44 Squamous cell carcinoma 41 Small cell carcinoma 15 Number of involved organs by metastasis Single organ 59 Multiple organs 41 Intrathoracic metastasis and brain were the most frequent sites of metastases, followed by the liver and bone, as shown in Table 2 . Other less frequent sites of metastasis were adrenal (4 cases) and skin (3 cases). Table 2 The associations between the site of metastasis and patients’ characteristics. Brain metastasis Intrathoracic metastasis Bone metastasis Liver metastasis present absent P value Present absent P value present absent P value present absent P value Smoking Never 9 24 0.58 6 27 0.75 8 25 0.007 8 25 0.161 Current 9 17 6 20 0 26 2 24 Gender Male 12 22 0.40 8 26 0.53 3 31 0.26 7 27 0.49 Female 6 19 4 12 5 20 3 22 Histopathology NSCLC 17 36 0.58 10 23 0.04 6 47 0.008 9 44 0.055 SCLC 1 5 2 4 2 4 1 5 PS 0–1 11 24 0.38 7 28 0.59 6 29 0.59 3 32 0.007 2–3 7 17 4 19 2 22 7 24 Comorbidity Present 10 18 0.27 8 20 0.12 3 25 0.41 4 24 0.73 Absent 8 23 4 27 8 26 6 25 Regarding the correlation between metastatic locations and patient characteristics, the clinicopathological aspects of various metastasis sites were analyzed using the Chi-square (χ2) test. No significant associations were found between the sites of distant metastasis and patient sex, or the presence of comorbidities. However, bone metastasis was found to be more frequent in NSCLC than SCLC, and liver metastases were significantly associated with a poor PS of 2–3 (p < 0.05) (Table 2 ) The median survival of the included metastatic lung cancer cases was 15.7 months, ranging from 3 to 31months. There was no significant difference in the overall survival between the sexes (p = 0.342). Likewise, there was no significant association between the overall survival and the types of histopathology. The mean survival time of patients with adenocarcinoma and squamous cell carcinoma was 16.6 months and 18.8 months, respectively, while it was 20.9 months for small-cell lung cancer cases. Figure (1): Kaplan-Meier curve of overall survival based on the number of involved organs by metastasis. Figure (2): Kaplan-Meier curve of overall survival based on the presence of brain metastasis. Median survival time is 19 months, (p = 0.81). Figure (3): Kaplan-Meier curve of overall survival based on the presence of liver metastasis. Median survival time is 10 months, (P < 0.001). Figure (4): Kaplan-Meier curve of overall survival based on the presence of bone metastasis. Median survival time is 26 months, (P = 0.011). Figure (5): Kaplan-Meier curve of overall survival based on the presence of intrathoracic metastasis. Median survival time is 29 months, (p = 0.214). Kaplan-Meier test showed that patients with multiorgan metastases had significantly shorter overall survival compared with those patients with single organ metastasis (Fig. 1). The mean survival time for the included cases with isolated brain metastasis was 20.9 months (ranging from 18.9–22.8, SD = 0.9, Fig. 2), while it was 11. 8 months for liver-only metastasis (ranging from 8.6–15.0 months, SD = 1.6, Fig. 3). The mean survival time was 27.1 months for patients with bone-only metastasis (ranging from 24.8–29.2, SD = 10.1, Fig. 4), which is significantly longer than the overall survival for patients with other sites of metastasis. For patients with intrathoracic metastasis, it was 25.5 months (ranging from 21.8–29.3 months, SD = 1.9, Fig. 5). Patients who had metastases to the liver had a lower survival rate than those who did not (P < 0.001) (Fig. 3). The occurrence of liver metastases was linked to a lower survival rate, not only according to the univariate analysis (HR = 2.081, P < 0.001) but also in a multivariate analysis using the Cox proportional hazards model (HR = 2.438, p < 0.001) as shown in table (3). Table (3): Multivariant cox proportional hazard analysis of overall survival for patients with metastatic lung cancer with different sites of metastasis. Variable 95% CI HR P value Metastatic organ Lower Upper Intrathoracic reference Liver .022 .348 2.438 .001 Bone .718 8.941 .930 .148 Brain .220 1.754 .477 .368 Discussion One common clinical issue is distant metastases at the time of lung cancer diagnosis. According to reports, 30–40% of NSCLC patients, and 60% of patients with SCLC have metastases at the time of diagnosis. Therefore, understanding the patterns of distant metastases is essential for tailoring treatment strategies and optimizing follow-up. ( 15 , 16 ) In our prospective study, adenocarcinoma was the most common histological subtype among patients with metastatic lung cancer. This is generally consistent with global reports that showed how the incidence of various tumour subtypes has altered recently, with lung adenocarcinoma currently outnumbering squamous cell carcinoma since 1990. ( 17 , 18 ) This change has been related to the awareness programs and the subsequent reduction in smoking rates. (l9) According to earlier population-based research, the prognosis for several metastatic malignancies varies depending on where the metastases occur. ( 20 , 21 , 22 ) Nonetheless, there is an ongoing debate on the prognostic significance of metastatic locations in metastatic lung cancer. While some studies found no correlation between survival and the site of involvement ( 23 ) , other researcher found that metastasis to particular organs seem to have an impact on prognosis in lung cancer ( 1 ) . We found that both NSCLC and SCLC commonly present with multiple organ metastases at diagnosis. Intrathoracic and brain metastasis were the most frequent sites, followed by liver and bone metastasis. This finding aligns with a previous study that also identified intrathoracic and brain metastasis as the most frequent sites of metastasis ( 24 ) . However, it differs from other studies reporting liver and bone as the most frequent sites ( 1 , 8 ) . These discrepancies may be attributed to differences in study populations or diagnostic imaging protocols. For instance, studies focusing on advanced-stage patients or utilizing more sensitive imaging modalities such as PET-CT may be more likely to detect bone or intrathoracic metastases. Additionally, regional differences in healthcare access or screening practices could influence the pattern of metastasis at presentation. Lastly, biological differences between tumor subtypes or molecular profiles could contribute to preferential metastatic spread, which might vary across cohorts. ( 25 ) Most of the previous studies reported that brain metastases are common in lung cancer at the time of initial diagnosis ( 26 , 27 ) . Additionally, 91% of patients with lung cancer develop brain metastasis within a year of their original diagnosis, with 10% being asymptomatic ( 28 ) . Interestingly, we found improvement in the overall survival of metastatic lung cancer patients when compared with the previously reported survival. ( 29 ) This is consistent with the results of three French consecutive nationwide prospective cohorts' studies. In these studies, comparing to 2020, the early mortality rate for metastatic NSCLC improved from 33.4% in 2000 to 29.2% in 2020, and for SCLC, from 30.7% in 2000 to 24.8% in 2020. ( 30 ) This suggests some progress in lung cancer management, mainly due to the emergence of molecular targeted therapy in recent years because of a better knowledge of the genetic alterations linked to lung cancer. ( 31 ) This is in addition to the development of radiofrequency ablation ( 32 ) , and customized treatment programs, which have shown better response rates and fewer side effects. These advancements are particularly relevant, as adenocarcinoma cases have become more common than squamous cell carcinoma. ( 33 , 34 ) This study's survival analysis highlighted the prognostic significance of metastasis sites. Patients with intrathoracic metastases had the best overall survival, followed by those with bone and brain metastases. The poorest survival rates were observed in patients with liver metastases. Earlier research ( 1 , 35 ) , also suggested that lung metastases had the best prognosis among metastatic lung cancer cases, while liver metastases remained the most unfavorable site. While brain metastasis in our study was not associated with shorter survival compared with other metastatic sites, in 1988, Sorensen, et al reported that the median survival after the onset of brain metastases in patients with inoperable adenocarcinoma of the lung was 73 days. The survival was significantly shorter for these patients than for those without this complication at various time points after treatment initiation ( 36 ) . In a recent Nature scientific report on patients with NSCLC who initially presented with brain metastasis, the median overall survival was 29 months (95% CI, 25.2–33.0). ( 37 ) The disparity between current and older survival outcomes can be attributed to the advancement in treatment modalities for patients with brain metastases in recent years, particularly after the development of stereotactic radiotherapy ( 38 ) . Additionally, recent studies have shown that immunotherapy and tailored therapy have offered significant benefit for patients with brain metastasis ( 39 , 40 ) . In contrast, there has been limited progress in the treatment of hepatic metastasis, which are commonly observed in lung cancer. These metastases typically respond poorly to both chemotherapy and immunotherapy ( 41 , 42 ) . Additionally, patients with hepatic metastases often experience poor tolerance to chemotherapy, particularly when liver function is compromised ( 43 ) . Autopsy studies of lung cancer patients have shown that over one-third of individuals had liver metastases, often associated with widespread metastases throughout the liver parenchyma, leading to hepatic insufficiency. ( 8 ) Moreover, when comparing patients with multiorgan metastases to those with a single metastasis, the latter group had a significantly better prognosis. Previous research has shown similar findings ( 8 , 44 ), concluding that the prognosis is the poorest for patients with NSCLC and SCLC who have multiple metastases. In a study conducted in 2015, patients with a single extrathoracic metastasis had a mean survival of 11.4 months, compared to 6.3 months for those with multiple metastases ( 44 ) . A recent Swiss study analyzing patients with metastatic NSCLC found that patients with metastases in three or more organs had a median survival of 5.6 months, while those with metastases in one or two organs had a median survival of 11.3 months. This difference was statistically significant, highlighting the impact of metastatic burden on survival outcomes. ( 45 ) This observation has been considered in the American Joint Committee on Cancer staging system ( 12 ), which indicates that patients with one extrathoracic metastasis have a better prognosis than those with multiple metastases. Conclusion We conclude that among patients with distant metastases, those with lung cancer and intrathoracic metastases have the best survival rates, while those with liver metastases have the poorest outcomes. Therefore, when developing treatment plans for metastatic lung cancer, it is crucial to consider this variation in survival on metastatic sites to ensure a more tailored and effective approach. Declarations Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article. Author Contribution The authors (Alya A. Al Zobair, Rami M. Adil Al-Hayali, Ahmed Ali Albakr) participated in data collection and wrote the manuscript. Data Availability The datasets used and analyzed during the current study available from the corresponding author on request. References Li, J., Zhu, H., Sun, L., Xu, W. & Wang, X. Prognostic value of site-specific metastases in lung cancer: A population based study. J Cancer 10 , 3079‒3086 (2019). Al Zobair, A.A., Jasim, B.I., AL Obeidy, B.F. & Jawher, N.M.T. Prognostic impact of hormone and HER2 status on prognosis of breast cancer in Mosul. Ann Trop & Public Health 23 , 844‒854 (2020). Ferlay, J. et al . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136 , E359‒386 (2012). Ambroggi, M. et al . Can early palliative care with anticancer treatment improve overall survival and patient-related outcomes in advanced lung cancer patients? A review of the literature. Support Care Cancer 26 , 2945‒2953 (2018). Wang, Y., Xie, S. & He, B.: Effect of EGFR gene polymorphism on efficacy of chemotherapy combined with targeted therapy for non‑small cell lung cancer in Chinese patients. Am J Cancer Res 9 , 619‒627 (2019). Cheng, Y., Zhang, T. & Xu, Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. MedComm (2020) 2 , 692‒729 (2021). Howlader, N. et al . editors. SEER Cancer Statistics Review, 1975-2013. National Cancer Institute. Bethesda, MD, based on November 2015 SEER data submission, posted to the SEER web site, (2016). Milovanovic, I.S., Stjepanovic, M. & Mitrovic, D. Distribution patterns of the metastases of the lung carcinoma in relation to histological type of the primary tumor: An autopsy study. Ann Thorac Med 12 , 191‒198 (2017). Tsai, H. C., Huang, J. Y., Hsieh, M. Y. & Wang, B. Y. Survival of Lung Cancer Patients by Histopathology in Taiwan from 2010 to 2016: A Nationwide Study. J Clin Med 11 , 5503 (2022). Riihimäki, M. et al . Metastatic sites and survival in lung cancer. Lung Cancer 86 , 78‒84 (2014). Nicholson, A. G. et al . The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol 17 , 362‒387 (2022). Rami-Porta, R. et al . Lung cancer staging: a concise update. Eur Respir J 51 , 1800190 (2018). Riely, G. J. et al . In: Non-Small Cell Lung Cancer. In: NCCN Clinical Practice Guidelines in Oncology. USA: National Comprehensive Cancer Network ; version 3 , 109‒119 (2025). Azam, F. et al . Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals. Case Rep Oncol 12 , 728–736 (2019). Matsuda, A. et al . Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 44 , 388‒396 (2014). Nakazawa, K. et al . Specific organ metastases and survival in small cell lung cancer. Oncol Lett 4 , 617‒620 (2012). Morita T. A statistical study of lung cancer in the annual of pathological autopsy cases in Japan, from 1958 to 1997, with reference to time trends of lung cancer in the world. Jpn J Cancer Res 93 , 15‒23 (2002) Yoshimi, I., Ohshima, A., Ajiki, W., Tsukuma, H. & Sobue, T. A comparison of trends in the incidence rate of lung cancer by histological type in the Osaka Cancer Registry, Japan and in the Surveillance, Epidemiology and End Results Program, USA. Jpn J Clin Oncol 33 , 98‒104 (2003). Lau, S. C. M., Pan, Y., Velcheti, V. & Wong, K. K. Squamous cell lung cancer: Current landscape and future therapeutic options. Cancer Cell 40 , 1279‒1293 (2022). Wu, S. G. et al . Sites of metastasis and overall survival in esophageal cancer: a population-based study. Cancer Manag Res 9 , 781‒788 (2017). Oweira, H. et al . Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis. World J Gastroenterol 23 , 1872‒1880 (2017). Dong, F. et al . Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study. Cancer Manag Res 9 , 611‒626 (2017). Paralkar, V. R., Li, T. & Langer, C. J. Population characteristics and prognostic factors in metastatic non-small-cell lung cancer: a Fox Chase Cancer Center retrospective. Clin Lung Cancer 9 , 116‒121 (2008). Tamura, T. et al . Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol 3 , 217‒221 (2015). Feng, Y. et al . The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study. Eur J Nucl Med Mol Imaging 51 , 3400‒3416 (2024). Fox, B. D., Cheung, V. J., Patel, A. J., Suki, D. & Rao, G. Epidemiology of metastatic brain tumors. Neurosurg Clin N Am 22 , 1–6 (2011). Hochstenbag, M. M., Twijnstra, A., Wilmink, J. T., Wouters, E. F. & ten Velde, G. P. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol 48 , 243–248 (2000). Schouten, L. J., Rutten, J, Huveneers, H. A. & Twijnstra, A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94 , 2698–2705 (2002) Debieuvre, D. et al . Study Group KBP-2020-CPHG; KBP-2020-CPHG. Lung cancer trends and tumor characteristic changes over 20 years (2000-2020): Results of three French consecutive nationwide prospective cohorts' studies. Lancet Reg Health Eur 22 , 100492 (2022). Debieuvre, D. et al . Lung cancer trends and tumor characteristic changes over 20 years (2000-2020): Results of three French consecutive nationwide prospective cohorts' studies. Lancet Reg Health Eur 22 , 100492 (2022). Salmani-Javan, E., Farhoudi, S. J. M. & Zarghami, N. Recent advances in molecular targeted therapy of lung cancer: Possible application in translation medicine. Iran J Basic Med Sci 27 , 122–133 (2024). Vaughn, C., Mychaskiw, G. & Sewell, P: Massive hemorrhage during radiofrequency ablation of a pulmonary neoplasm. Anesth Analg 94 , 1149–1151 (2002). Reck, M. & Rabe, K. F. Precision diagnosis and treatment for advanced non‑small‑cell lung cancer. N Engl J Med 377 , 849–861 (2017). Wang, B. Y. et al. The comparison between adenocarcinoma and squamous cell carcinoma in lung cancer patients. J Cancer Res Clin Oncol 146 , 43–52 (2020). Liao, Y., Fan, X. & Wang, X. Effects of different metastasis patterns, surgery and other factors on the prognosis of patients with stage IV non-small cell lung cancer: A Surveillance, Epidemiology, and End Results (SEER) linked database analysis. Oncol Lett 18 , 581–592 (2019). Sorensen, J. B., Hansen, H. H., Hansen, M. & Dombernowsky, P. Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis. J Clin Oncol 6 , 1474–1480 (1988). Kahraman, S. et al . Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases. Sci Rep 14 , 5820 (2024). Soliman, H., Das, S., Larson, D. A. & Sahgal, A. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases. Oncotarget 7 , 12318–12330 (2016). Wang, Z. , Yang, J. J. , Tu, H. Y. , Yan, H. H. & Wu, Y. L . Retrospective study on bevacizumab in the treatment of non-small cell lung cancer with brain metastases. Int J Clin Oncol 25 , 267-273 (2020). Zhuang, H., Shi, S. & Chang, J. Y. Treatment modes for EGFR mutations in patients with brain metastases from non-small cell lung cancer: controversy, causes, and solutions. Transl Lung Cancer Res 8 , 524–531 (2019). Di Carlo, I., Grasso, G., Patane' D, Russello, D. & Latteri, F. Liver metastases from lung cancer: Is surgical resection justified? Ann Thorac Surg 76 , 291–293 (2003). Gorg, C., Schwerk, W. B., Wolf, M. & Havemann, K. Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement. Bildgebung 57 : 70–73 (1990). Ćeriman, K. V. et al . Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases. Curr Issues Mol Biol 46 , 13443‒13455 (2024). Eberhardt, W. E. et al . The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol 10 , 1515‒1522 (2015). Wallrabenstein, T., Del Rio, J., Templeton, A. J. & Buess, M. Much has changed in the last decade except overall survival: A Swiss single center analysis of treatment and survival in patients with stage IV non-small cell lung cancer. PLoS One 15 , e0233768 (2020). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9033388","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":639758974,"identity":"8b1dcf19-cf20-41eb-8934-15fc2973745f","order_by":0,"name":"Alya Al Zobair","email":"data:image/png;base64,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","orcid":"","institution":"University of Mosul","correspondingAuthor":true,"prefix":"","firstName":"Alya","middleName":"Al","lastName":"Zobair","suffix":""},{"id":639758977,"identity":"d5d6644d-6e4f-4bd6-9a6e-ab19732aa14e","order_by":1,"name":"Rami Al Hayali","email":"","orcid":"","institution":"University of Mosul","correspondingAuthor":false,"prefix":"","firstName":"Rami","middleName":"Al","lastName":"Hayali","suffix":""},{"id":639758981,"identity":"6cba1e88-014b-47ad-955c-ef0c0d31c1a7","order_by":2,"name":"Ahmed Ali Albakr","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Ali","lastName":"Albakr","suffix":""}],"badges":[],"createdAt":"2026-03-04 19:24:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9033388/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9033388/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109303946,"identity":"d3b5a8db-5bb2-449c-a193-4ad3c903132b","added_by":"auto","created_at":"2026-05-15 09:41:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":37218,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival based on the number of involved organs by metastasis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/7236c444b47d0edcb0610039.png"},{"id":109303947,"identity":"dea9a6cd-2be4-4d15-8eca-7411ec70168f","added_by":"auto","created_at":"2026-05-15 09:41:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":40853,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival based on the presence of brain metastasis. Median survival time is 19 months, (p= 0.81).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/411fb5d547f28233ac91dd48.png"},{"id":109303906,"identity":"dad6fe9f-6b33-498b-8141-8f333dab7135","added_by":"auto","created_at":"2026-05-15 09:41:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41262,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival based on the presence of liver metastasis. Median survival time is 10 months, (P\u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/3e0d50cf4c566e99905a2160.png"},{"id":109303907,"identity":"1171dcae-b0a2-4f57-bed5-7764ebdaea01","added_by":"auto","created_at":"2026-05-15 09:41:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":42477,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival based on the presence of bone metastasis. Median survival time is 26 months, (P= 0.011).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/794287415074cc9e7c209a57.png"},{"id":109303948,"identity":"79e6e495-b0f5-4938-816d-6166f52d5903","added_by":"auto","created_at":"2026-05-15 09:41:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":41829,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of overall survival based on the presence of intrathoracic metastasis. Median survival time is 29 months, (p=0.214).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/361d149c1f3a40ecc4de6994.png"},{"id":109441092,"identity":"efbe9351-39c6-4311-814e-e78267cd6165","added_by":"auto","created_at":"2026-05-18 07:12:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":468072,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9033388/v1/14385b47-4e6a-4930-8eea-b529029ade09.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe Impact of Some Clinicopathological Factors on the Overall Survival in Metastatic Lung Cancer\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast and lung cancers are the most prevalent cancers worldwide; however, lung cancer remains the leading cause of cancer-related mortality globally \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e. Unfortunately, more than half of lung cancer patients are diagnosed at an advanced stage due to the lack of screening programs in most developed and developing nations\u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/sup\u003e. The estimated overall survival following the diagnosis of metastasis was less than 12 months until a few years ago, and it is usually associated with a poor quality of life and high burden of symptoms \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAdvancements in cancer treatment, including immunotherapy and molecular targeted therapy, offer substitutes for the standard forms of radiation and chemotherapy; however, metastatic lung cancer is still an incurable condition \u003csup\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e),\u003c/sup\u003e and only 4.9% of people survive for five years \u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe most frequent metastatic sites in patients with advanced lung cancer at the time of diagnosis or during follow-up are the liver, bone, adrenal, and central nervous system\u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe World Health Organization (WHO) lists squamous cell carcinoma, adenocarcinoma, small-cell carcinoma, and large-cell carcinoma as the most frequent primary histological types of lung cancer. The biological characteristics and prognosis of these histological types vary, with small-cell lung cancer (SCLC) frequently being contrasted with the three remaining non-small-cell lung cancers (NSCLCs)\u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e. Genetic testing plays a crucial role in precisely identifying lung cancer subtypes, enabling more targeted and effective treatment strategies that enhance therapeutic outcomes\u003csup\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSex, histological subtype, and age at diagnosis may affect the metastatic locations and survival in metastatic lung cancer \u003csup\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/sup\u003e. Due to the disparities in biological differences and treatment techniques, the survival of patients with distinct metastatic locations varies. For this reason, understanding the metastatic patterns is essential to adjusting the therapy and monitoring plans, hence, this study aims to assess how distant organ metastases, clinical characteristics, and pathological variables affect lung cancer patients' overall survival.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eThis is a prospective survival study conducted on patients with metastatic lung cancer who were diagnosed in the period between first Jan, 2020 and first Jan, 2022 and received treatment at Mosul Oncology Hospital in Iraq. Pathological specimens were analyzed to confirm lung cancer diagnoses in all patients, and the classification of pathological diagnoses was conducted according to the WHO classification \u003csup\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e The study was approved by the Scientific Committee of the College of Medicine, University of Mosul, and conducted in accordance with the Helsinki Declaration, written informed consent was obtained from all participants before their enrollment in the study.\u003c/p\u003e \u003cp\u003eInclusion criteria included the following:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients diagnosed with stage IV (metastatic) primary lung cancer\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHaving histological types limited to adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell carcinoma\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eLung cancer is the only primary tumor.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eExclusion criteria:\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with incomplete data.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients who were lost to follow-up.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHistopathological diagnosis other than the above-mentioned types.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eAll the patients had a staging workup that included a computed tomography (CT) scan of the chest, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the brain. Bone scintigraphy as well as positron emission tomography/computed tomography (PET/CT) scan were done for selected cases.\u003c/p\u003e \u003cp\u003eThe eighth edition of the American Joint Committee on Cancer (AJCC) staging manual was used to stage the patients. Treatment was given according to the National Comprehensive Cancer Network (NCCN) guidelines \u003csup\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/sup\u003e. Patients' clinicopathological characteristics were documented, including age, performance status (PS) at diagnosis (ECOG scoring system), comorbidities, sites of metastasis, histological type, and molecular subtypes. \u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe patients were identified as having a single or multiple metastases. Metastatic sites were either intrathoracic metastases, including patients with separate tumor nodules in a contralateral lobe, pleural nodules, pleural effusion, or pericardial effusion, or extrathoracic metastases involving the liver, bone, brain, adrenal gland, or other organ\u003c/p\u003e \u003cp\u003eAll patients were monitored regularly every 1\u0026ndash;3 months for a minimum of 20 months. For each patient, the date of death or the last follow-up visit since diagnosis was recorded.\u003c/p\u003e \u003cp\u003eStatistical analysis and data management were done using Version 20, SPSS. Survival analysis was used to estimate the impact of the site of metastasis and other clinical and pathological factors on the patient's survival.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOne hundred patients with metastatic lung cancer were included in this study. Their mean age was 63.7 years, ranging from 45\u0026ndash;81 years, of whom 65% were male and 35% were female. The mean age of the included male patients was 65 years, ranging from 53 to 81 years, while the mean age of the included female patients was 60 years, ranging from 45 to 77 years.\u003c/p\u003e \u003cp\u003eSeventy-five percent of the male patients were current or x-smokers, a significantly higher proportion compared to 45% of female patients. At the time of metastatic lung cancer diagnosis, 46% of patients had comorbidities, including hypertension, diabetes mellitus, ischemic heart disease, and others, with hypertension being the most common. The majority of patients (55%) had a good performance status at diagnosis (ECOG PS 0\u0026ndash;1).\u003c/p\u003e \u003cp\u003eNSCLC represented 85% of cases, and adenocarcinoma was the most frequent histopathological subtype of lung cancer, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical, demographic and histopathological characteristics of the included patients with metastatic lung cancer.\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent or former smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eECOG PS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmall cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of involved organs by metastasis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle organ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple organs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41\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\u003eIntrathoracic metastasis and brain were the most frequent sites of metastases, followed by the liver and bone, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Other less frequent sites of metastasis were adrenal (4 cases) and skin (3 cases).\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\u003eThe associations between the site of metastasis and patients\u0026rsquo; characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBrain metastasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eIntrathoracic metastasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eBone metastasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c13\" namest=\"c11\"\u003e \u003cp\u003eLiver metastasis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003epresent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eabsent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eabsent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003epresent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eabsent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003epresent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eabsent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistopathology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSCLC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCLC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e25\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\u003eRegarding the correlation between metastatic locations and patient characteristics, the clinicopathological aspects of various metastasis sites were analyzed using the Chi-square (χ2) test. No significant associations were found between the sites of distant metastasis and patient sex, or the presence of comorbidities. However, bone metastasis was found to be more frequent in NSCLC than SCLC, and liver metastases were significantly associated with a poor PS of 2\u0026ndash;3 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe median survival of the included metastatic lung cancer cases was 15.7 months, ranging from 3 to 31months. There was no significant difference in the overall survival between the sexes (p\u0026thinsp;=\u0026thinsp;0.342). Likewise, there was no significant association between the overall survival and the types of histopathology.\u003c/p\u003e \u003cp\u003eThe mean survival time of patients with adenocarcinoma and squamous cell carcinoma was 16.6 months and 18.8 months, respectively, while it was 20.9 months for small-cell lung cancer cases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure (1): Kaplan-Meier curve of overall survival based on the number of involved organs by metastasis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure (2): Kaplan-Meier curve of overall survival based on the presence of brain metastasis. Median survival time is 19 months, (p\u0026thinsp;=\u0026thinsp;0.81).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure (3): Kaplan-Meier curve of overall survival based on the presence of liver metastasis. Median survival time is 10 months, (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure (4): Kaplan-Meier curve of overall survival based on the presence of bone metastasis. Median survival time is 26 months, (P\u0026thinsp;=\u0026thinsp;0.011).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eFigure (5): Kaplan-Meier curve of overall survival based on the presence of intrathoracic metastasis. Median survival time is 29 months, (p\u0026thinsp;=\u0026thinsp;0.214).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eKaplan-Meier test showed that patients with multiorgan metastases had significantly shorter overall survival compared with those patients with single organ metastasis (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe mean survival time for the included cases with isolated brain metastasis was 20.9 months (ranging from 18.9\u0026ndash;22.8, SD\u0026thinsp;=\u0026thinsp;0.9, Fig.\u0026nbsp;2), while it was 11. 8 months for liver-only metastasis (ranging from 8.6\u0026ndash;15.0 months, SD\u0026thinsp;=\u0026thinsp;1.6, Fig.\u0026nbsp;3). The mean survival time was 27.1 months for patients with bone-only metastasis (ranging from 24.8\u0026ndash;29.2, SD\u0026thinsp;=\u0026thinsp;10.1, Fig.\u0026nbsp;4), which is significantly longer than the overall survival for patients with other sites of metastasis. For patients with intrathoracic metastasis, it was 25.5 months (ranging from 21.8\u0026ndash;29.3 months, SD\u0026thinsp;=\u0026thinsp;1.9, Fig.\u0026nbsp;5).\u003c/p\u003e \u003cp\u003ePatients who had metastases to the liver had a lower survival rate than those who did not (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;3). The occurrence of liver metastases was linked to a lower survival rate, not only according to the univariate analysis (HR\u0026thinsp;=\u0026thinsp;2.081, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) but also in a multivariate analysis using the Cox proportional hazards model (HR\u0026thinsp;=\u0026thinsp;2.438, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as shown in table (3).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(3): Multivariant cox proportional hazard analysis of overall survival for patients with metastatic lung cancer with different sites of metastasis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetastatic organ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrathoracic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ereference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.348\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.941\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.368\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\u003eOne common clinical issue is distant metastases at the time of lung cancer diagnosis. According to reports, 30\u0026ndash;40% of NSCLC patients, and 60% of patients with SCLC have metastases at the time of diagnosis. Therefore, understanding the patterns of distant metastases is essential for tailoring treatment strategies and optimizing follow-up. \u003csup\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn our prospective study, adenocarcinoma was the most common histological subtype among patients with metastatic lung cancer. This is generally consistent with global reports that showed how the incidence of various tumour subtypes has altered recently, with lung adenocarcinoma currently outnumbering squamous cell carcinoma since 1990. \u003csup\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/sup\u003e This change has been related to the awareness programs and the subsequent reduction in smoking rates. \u003csup\u003e(l9)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAccording to earlier population-based research, the prognosis for several metastatic malignancies varies depending on where the metastases occur. \u003csup\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/sup\u003e Nonetheless, there is an ongoing debate on the prognostic significance of metastatic locations in metastatic lung cancer. While some studies found no correlation between survival and the site of involvement \u003csup\u003e(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/sup\u003e\u003csub\u003e,\u003c/sub\u003e other researcher found that metastasis to particular organs seem to have an impact on prognosis in lung cancer \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe found that both NSCLC and SCLC commonly present with multiple organ metastases at diagnosis. Intrathoracic and brain metastasis were the most frequent sites, followed by liver and bone metastasis. This finding aligns with a previous study that also identified intrathoracic and brain metastasis as the most frequent sites of metastasis\u003csup\u003e(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/sup\u003e. However, it differs from other studies reporting liver and bone as the most frequent sites \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e. These discrepancies may be attributed to differences in study populations or diagnostic imaging protocols. For instance, studies focusing on advanced-stage patients or utilizing more sensitive imaging modalities such as PET-CT may be more likely to detect bone or intrathoracic metastases. Additionally, regional differences in healthcare access or screening practices could influence the pattern of metastasis at presentation. Lastly, biological differences between tumor subtypes or molecular profiles could contribute to preferential metastatic spread, which might vary across cohorts. \u003csup\u003e(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMost of the previous studies reported that brain metastases are common in lung cancer at the time of initial diagnosis \u003csup\u003e(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/sup\u003e. Additionally, 91% of patients with lung cancer develop brain metastasis within a year of their original diagnosis, with 10% being asymptomatic \u003csup\u003e(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eInterestingly, we found improvement in the overall survival of metastatic lung cancer patients when compared with the previously reported survival. \u003csup\u003e(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/sup\u003e This is consistent with the results of three French consecutive nationwide prospective cohorts' studies. In these studies, comparing to 2020, the early mortality rate for metastatic NSCLC improved from 33.4% in 2000 to 29.2% in 2020, and for SCLC, from 30.7% in 2000 to 24.8% in 2020. \u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e This suggests some progress in lung cancer management, mainly due to the emergence of molecular targeted therapy in recent years because of a better knowledge of the genetic alterations linked to lung cancer. \u003csup\u003e(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/sup\u003e This is in addition to the development of radiofrequency ablation \u003csup\u003e(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/sup\u003e\u003csub\u003e,\u003c/sub\u003e and customized treatment programs, which have shown better response rates and fewer side effects. These advancements are particularly relevant, as adenocarcinoma cases have become more common than squamous cell carcinoma. \u003csup\u003e(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study's survival analysis highlighted the prognostic significance of metastasis sites. Patients with intrathoracic metastases had the best overall survival, followed by those with bone and brain metastases. The poorest survival rates were observed in patients with liver metastases. Earlier research \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/sup\u003e, also suggested that lung metastases had the best prognosis among metastatic lung cancer cases, while liver metastases remained the most unfavorable site.\u003c/p\u003e \u003cp\u003eWhile brain metastasis in our study was not associated with shorter survival compared with other metastatic sites, in 1988, Sorensen, et al reported that the median survival after the onset of brain metastases in patients with inoperable adenocarcinoma of the lung was 73 days. The survival was significantly shorter for these patients than for those without this complication at various time points after treatment initiation \u003csup\u003e(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/sup\u003e. In a recent Nature scientific report on patients with NSCLC who initially presented with brain metastasis, the median overall survival was 29 months (95% CI, 25.2\u0026ndash;33.0). \u003csup\u003e(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe disparity between current and older survival outcomes can be attributed to the advancement in treatment modalities for patients with brain metastases in recent years, particularly after the development of stereotactic radiotherapy \u003csup\u003e(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e)\u003c/sup\u003e. Additionally, recent studies have shown that immunotherapy and tailored therapy have offered significant benefit for patients with brain metastasis \u003csup\u003e(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn contrast, there has been limited progress in the treatment of hepatic metastasis, which are commonly observed in lung cancer. These metastases typically respond poorly to both chemotherapy and immunotherapy \u003csup\u003e(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e)\u003c/sup\u003e. Additionally, patients with hepatic metastases often experience poor tolerance to chemotherapy, particularly when liver function is compromised \u003csup\u003e(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e)\u003c/sup\u003e. Autopsy studies of lung cancer patients have shown that over one-third of individuals had liver metastases, often associated with widespread metastases throughout the liver parenchyma, leading to hepatic insufficiency. \u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMoreover, when comparing patients with multiorgan metastases to those with a single metastasis, the latter group had a significantly better prognosis. Previous research has shown similar findings \u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e),\u003c/sup\u003e concluding that the prognosis is the poorest for patients with NSCLC and SCLC who have multiple metastases. In a study conducted in 2015, patients with a single extrathoracic metastasis had a mean survival of 11.4 months, compared to 6.3 months for those with multiple metastases \u003csup\u003e(\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e)\u003c/sup\u003e. A recent Swiss study analyzing patients with metastatic NSCLC found that patients with metastases in three or more organs had a median survival of 5.6 months, while those with metastases in one or two organs had a median survival of 11.3 months. This difference was statistically significant, highlighting the impact of metastatic burden on survival outcomes. \u003csup\u003e(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e)\u003c/sup\u003e This observation has been considered in the American Joint Committee on Cancer staging system \u003csup\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e),\u003c/sup\u003e which indicates that patients with one extrathoracic metastasis have a better prognosis than those with multiple metastases.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe conclude that among patients with distant metastases, those with lung cancer and intrathoracic metastases have the best survival rates, while those with liver metastases have the poorest outcomes. Therefore, when developing treatment plans for metastatic lung cancer, it is crucial to consider this variation in survival on metastatic sites to ensure a more tailored and effective approach.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe authors (Alya A. Al Zobair, Rami M. Adil Al-Hayali, Ahmed Ali Albakr) participated in data collection and wrote the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed during the current study available from the corresponding author on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLi, J., Zhu, H., Sun, L., Xu, W. \u0026amp; Wang, X. Prognostic value of site-specific metastases in lung cancer: A population based study. \u003cem\u003eJ Cancer\u003c/em\u003e\u003cstrong\u003e10\u003c/strong\u003e, 3079‒3086 (2019).\u003c/li\u003e\n \u003cli\u003eAl Zobair, A.A., Jasim, B.I., AL Obeidy, B.F. \u0026amp; Jawher, N.M.T. Prognostic impact of hormone and HER2 status on prognosis of breast cancer in Mosul. \u003cem\u003eAnn Trop \u0026amp; Public Health\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;23\u003c/strong\u003e, 844‒854 (2020).\u003c/li\u003e\n \u003cli\u003eFerlay, J. \u003cem\u003eet al\u003c/em\u003e. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. \u003cem\u003eInt J Cancer\u003c/em\u003e\u003cstrong\u003e136\u003c/strong\u003e, E359‒386 (2012).\u003c/li\u003e\n \u003cli\u003eAmbroggi, M. \u003cem\u003eet al\u003c/em\u003e. Can early palliative care with anticancer treatment improve overall survival and patient-related outcomes in advanced lung cancer patients? A review of the literature. \u003cem\u003eSupport Care Cancer\u003c/em\u003e\u003cstrong\u003e26\u003c/strong\u003e, 2945‒2953 (2018).\u003c/li\u003e\n \u003cli\u003eWang, Y., Xie, S. \u0026amp; He, B.: Effect of EGFR gene polymorphism on efficacy of chemotherapy combined with targeted therapy for non‑small cell lung cancer in Chinese patients. \u003cem\u003eAm J Cancer Res\u003c/em\u003e\u003cstrong\u003e9\u003c/strong\u003e, 619‒627 (2019).\u003c/li\u003e\n \u003cli\u003eCheng, Y., Zhang, T. \u0026amp; Xu, Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. \u003cem\u003eMedComm (2020)\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e2\u003c/strong\u003e, 692‒729 (2021).\u003c/li\u003e\n \u003cli\u003eHowlader, N. \u003cem\u003eet al\u003c/em\u003e. editors. SEER Cancer Statistics Review, 1975-2013. National Cancer Institute. Bethesda, MD, based on November 2015 SEER data submission, posted to the SEER web site, (2016).\u003c/li\u003e\n \u003cli\u003eMilovanovic, I.S., Stjepanovic, M. \u0026amp; Mitrovic, D. Distribution patterns of the metastases of the lung carcinoma in relation to histological type of the primary tumor: An autopsy study. \u003cem\u003eAnn Thorac Med\u003c/em\u003e\u003cstrong\u003e12\u003c/strong\u003e, 191‒198 (2017).\u003c/li\u003e\n \u003cli\u003eTsai, H. C., Huang, J. Y., Hsieh, M. Y. \u0026amp; Wang, B. Y. Survival of Lung Cancer Patients by Histopathology in Taiwan from 2010 to 2016: A Nationwide Study. \u003cem\u003eJ Clin Med\u003c/em\u003e\u003cstrong\u003e11\u003c/strong\u003e, 5503 (2022).\u003c/li\u003e\n \u003cli\u003eRiihim\u0026auml;ki, M. \u003cem\u003eet al\u003c/em\u003e. Metastatic sites and survival in lung cancer. \u003cem\u003eLung Cancer\u003c/em\u003e\u003cstrong\u003e86\u003c/strong\u003e, 78‒84 (2014).\u003c/li\u003e\n \u003cli\u003eNicholson, A. G. \u003cem\u003eet al\u003c/em\u003e. The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. \u003cem\u003eJ Thorac Oncol\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e17\u003c/strong\u003e, 362‒387 (2022).\u003c/li\u003e\n \u003cli\u003eRami-Porta, R. \u003cem\u003eet al\u003c/em\u003e. Lung cancer staging: a concise update. \u003cem\u003eEur Respir J\u003c/em\u003e\u003cstrong\u003e51\u003c/strong\u003e, 1800190 (2018).\u003c/li\u003e\n \u003cli\u003eRiely, G. J. \u003cem\u003eet al\u003c/em\u003e. In: Non-Small Cell Lung Cancer. In: NCCN Clinical Practice Guidelines in Oncology. USA: \u003cem\u003eNational Comprehensive Cancer Network\u003c/em\u003e; version \u003cstrong\u003e3\u003c/strong\u003e, 109‒119 (2025).\u003c/li\u003e\n \u003cli\u003eAzam, F. \u003cem\u003eet al\u003c/em\u003e. Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals. \u003cem\u003eCase Rep Oncol\u003c/em\u003e\u003cstrong\u003e12\u003c/strong\u003e, 728\u0026ndash;736 (2019).\u003c/li\u003e\n \u003cli\u003eMatsuda, A. \u003cem\u003eet al\u003c/em\u003e. Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. \u003cem\u003eJpn J Clin Oncol\u003c/em\u003e\u003cstrong\u003e44\u003c/strong\u003e, 388‒396 (2014).\u003c/li\u003e\n \u003cli\u003eNakazawa, K. \u003cem\u003eet al\u003c/em\u003e. Specific organ metastases and survival in small cell lung cancer. \u003cem\u003eOncol Lett\u003c/em\u003e\u003cstrong\u003e4\u003c/strong\u003e, 617‒620 (2012).\u003c/li\u003e\n \u003cli\u003eMorita T. A statistical study of lung cancer in the annual of pathological autopsy cases in Japan, from 1958 to 1997, with reference to time trends of lung cancer in the world. \u003cem\u003eJpn J Cancer Res\u003c/em\u003e\u003cstrong\u003e93\u003c/strong\u003e, 15‒23 (2002)\u003c/li\u003e\n \u003cli\u003eYoshimi, I., Ohshima, A., Ajiki, W., Tsukuma, H. \u0026amp; Sobue, T. A comparison of trends in the incidence rate of lung cancer by histological type in the Osaka Cancer Registry, Japan and in the Surveillance, Epidemiology and End Results Program, USA. \u003cem\u003eJpn J Clin Oncol\u003c/em\u003e\u003cstrong\u003e33\u003c/strong\u003e, 98‒104 (2003).\u003c/li\u003e\n \u003cli\u003eLau, S. C. M., Pan, Y., Velcheti, V. \u0026amp; Wong, K. K. Squamous cell lung cancer: Current landscape and future therapeutic options. \u003cem\u003eCancer Cell\u003c/em\u003e\u003cstrong\u003e40\u003c/strong\u003e, 1279‒1293 (2022).\u003c/li\u003e\n \u003cli\u003eWu, S. G. \u003cem\u003eet al\u003c/em\u003e. Sites of metastasis and overall survival in esophageal cancer: a population-based study. \u003cem\u003eCancer Manag Res\u003c/em\u003e\u003cstrong\u003e9\u003c/strong\u003e, 781‒788 (2017).\u003c/li\u003e\n \u003cli\u003eOweira, H. \u003cem\u003eet al\u003c/em\u003e. Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis. \u003cem\u003eWorld J Gastroenterol\u003c/em\u003e\u003cstrong\u003e23\u003c/strong\u003e, 1872‒1880 (2017).\u003c/li\u003e\n \u003cli\u003eDong, F. \u003cem\u003eet al\u003c/em\u003e. Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study. Cancer Manag Res \u003cstrong\u003e9\u003c/strong\u003e, 611‒626 (2017).\u003c/li\u003e\n \u003cli\u003eParalkar, V. R., Li, T. \u0026amp; Langer, C. J. Population characteristics and prognostic factors in metastatic non-small-cell lung cancer: a Fox Chase Cancer Center retrospective. \u003cem\u003eClin Lung Cancer\u003c/em\u003e\u003cstrong\u003e9\u003c/strong\u003e, 116‒121 (2008).\u003c/li\u003e\n \u003cli\u003eTamura, T. \u003cem\u003eet al\u003c/em\u003e. Specific organ metastases and survival in metastatic non-small-cell lung cancer. \u003cem\u003eMol Clin Oncol\u003c/em\u003e\u003cstrong\u003e3\u003c/strong\u003e, 217‒221 (2015).\u003c/li\u003e\n \u003cli\u003eFeng, Y. \u003cem\u003eet al\u003c/em\u003e. The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study. \u003cem\u003eEur J Nucl Med Mol Imaging\u003c/em\u003e\u003cstrong\u003e51\u003c/strong\u003e, 3400‒3416 (2024).\u003c/li\u003e\n \u003cli\u003eFox, B. D., Cheung, V. J., Patel, A. J., Suki, D. \u0026amp; Rao, G. Epidemiology of metastatic brain tumors. \u003cem\u003eNeurosurg Clin N Am\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, 1\u0026ndash;6 (2011).\u003c/li\u003e\n \u003cli\u003eHochstenbag, M. M., Twijnstra, A., Wilmink, J. T., Wouters, E. F. \u0026amp; ten Velde, G. P. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. \u003cem\u003eJ Neurooncol\u003c/em\u003e\u003cstrong\u003e48\u003c/strong\u003e, 243\u0026ndash;248 (2000).\u003c/li\u003e\n \u003cli\u003eSchouten, L. J., Rutten, J, Huveneers, H. A. \u0026amp; Twijnstra, A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. \u003cem\u003eCancer\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e94\u003c/strong\u003e, 2698\u0026ndash;2705 (2002)\u003c/li\u003e\n \u003cli\u003eDebieuvre, D. \u003cem\u003eet al\u003c/em\u003e. Study Group KBP-2020-CPHG; KBP-2020-CPHG. Lung cancer trends and tumor characteristic changes over 20 years (2000-2020): Results of three French consecutive nationwide prospective cohorts\u0026apos; studies. \u003cem\u003eLancet Reg Health Eur\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, 100492 (2022).\u003c/li\u003e\n \u003cli\u003eDebieuvre, D. \u003cem\u003eet al\u003c/em\u003e. Lung cancer trends and tumor characteristic changes over 20 years (2000-2020): Results of three French consecutive nationwide prospective cohorts\u0026apos; studies. \u003cem\u003eLancet Reg Health Eur\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, 100492 (2022).\u003c/li\u003e\n \u003cli\u003eSalmani-Javan, E., Farhoudi, S. J. M. \u0026amp; Zarghami, N. Recent advances in molecular targeted therapy of lung cancer: Possible application in translation medicine. \u003cem\u003eIran J Basic Med Sci\u003c/em\u003e\u003cstrong\u003e27\u003c/strong\u003e, 122\u0026ndash;133 (2024).\u003c/li\u003e\n \u003cli\u003eVaughn, C., Mychaskiw, G. \u0026amp; Sewell, P: Massive hemorrhage during radiofrequency ablation of a pulmonary neoplasm. \u003cem\u003eAnesth Analg\u003c/em\u003e\u003cstrong\u003e94\u003c/strong\u003e, 1149\u0026ndash;1151 (2002).\u003c/li\u003e\n \u003cli\u003eReck, M. \u0026amp; Rabe, K. F. Precision diagnosis and treatment for advanced non‑small‑cell lung cancer. \u003cem\u003eN Engl J Med\u003c/em\u003e\u003cstrong\u003e377\u003c/strong\u003e, 849\u0026ndash;861 (2017).\u003c/li\u003e\n \u003cli\u003eWang, B. Y.\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e The comparison between adenocarcinoma and squamous cell carcinoma in lung cancer patients. \u003cem\u003eJ Cancer Res Clin Oncol\u003c/em\u003e\u003cstrong\u003e146\u003c/strong\u003e, 43\u0026ndash;52 (2020).\u003c/li\u003e\n \u003cli\u003eLiao, Y., Fan, X. \u0026amp; Wang, X. Effects of different metastasis patterns, surgery and other factors on the prognosis of patients with stage IV non-small cell lung cancer: A Surveillance, Epidemiology, and End Results (SEER) linked database analysis. \u003cem\u003eOncol Lett\u003c/em\u003e\u003cstrong\u003e18\u003c/strong\u003e, 581\u0026ndash;592 (2019).\u003c/li\u003e\n \u003cli\u003eSorensen, J. B., Hansen, H. H., Hansen, M. \u0026amp; Dombernowsky, P. Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis. \u003cem\u003eJ Clin Oncol\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e6\u003c/strong\u003e, 1474\u0026ndash;1480 (1988).\u003c/li\u003e\n \u003cli\u003eKahraman, S. \u003cem\u003eet al\u003c/em\u003e. Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases. \u003cem\u003eSci Rep\u003c/em\u003e\u003cstrong\u003e14\u003c/strong\u003e, 5820 (2024).\u003c/li\u003e\n \u003cli\u003eSoliman, H., Das, S., Larson, D. A. \u0026amp; Sahgal, A. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases. \u003cem\u003eOncotarget\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e7\u003c/strong\u003e, 12318\u0026ndash;12330 (2016).\u003c/li\u003e\n \u003cli\u003eWang, Z.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, Yang, J. J.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, Tu, H. Y.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, Yan, H. H.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u0026amp; Wu, Y. L\u003csup\u003e.\u003c/sup\u003e Retrospective study on bevacizumab in the treatment of non-small cell lung cancer with brain metastases. \u003cem\u003eInt J Clin Oncol\u003c/em\u003e\u003cstrong\u003e25\u003c/strong\u003e, 267-273 (2020).\u003c/li\u003e\n \u003cli\u003eZhuang, H., Shi, S. \u0026amp; Chang, J. Y. Treatment modes for EGFR mutations in patients with brain metastases from non-small cell lung cancer: controversy, causes, and solutions. \u003cem\u003eTransl Lung Cancer Res\u003c/em\u003e\u003cstrong\u003e8\u003c/strong\u003e, 524\u0026ndash;531 (2019).\u003c/li\u003e\n \u003cli\u003eDi Carlo, I., Grasso, G., Patane\u0026apos; D, Russello, D. \u0026amp; Latteri, F. Liver metastases from lung cancer: Is surgical resection justified? \u003cem\u003eAnn Thorac Surg\u003c/em\u003e\u003cstrong\u003e76\u003c/strong\u003e, 291\u0026ndash;293 (2003).\u003c/li\u003e\n \u003cli\u003eGorg, C., Schwerk, W. B., Wolf, M. \u0026amp; Havemann, K. Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement. \u003cem\u003eBildgebung\u003c/em\u003e\u003cstrong\u003e57\u003c/strong\u003e: 70\u0026ndash;73 (1990).\u003c/li\u003e\n \u003cli\u003eĆeriman, K. V. \u003cem\u003eet al\u003c/em\u003e. Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases. \u003cem\u003eCurr Issues Mol Biol\u003c/em\u003e\u003cstrong\u003e46\u003c/strong\u003e, 13443‒13455 (2024).\u003c/li\u003e\n \u003cli\u003eEberhardt, W. E. \u003cem\u003eet al\u003c/em\u003e. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming eighth Edition of the TNM Classification of Lung Cancer. \u003cem\u003eJ Thorac Oncol\u003c/em\u003e\u003cstrong\u003e10\u003c/strong\u003e, 1515‒1522 (2015).\u003c/li\u003e\n \u003cli\u003eWallrabenstein, T., Del Rio, J., Templeton, A. J. \u0026amp; Buess, M. Much has changed in the last decade except overall survival: A Swiss single center analysis of treatment and survival in patients with stage IV non-small cell lung cancer. \u003cem\u003ePLoS One\u003c/em\u003e\u003cstrong\u003e15\u003c/strong\u003e, e0233768 (2020).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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":"","lastPublishedDoi":"10.21203/rs.3.rs-9033388/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9033388/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe survival of patients with distinct metastatic locations varies due to the disparities in biological heterogeneity and treatment techniques. This study aims to assess how distant organ metastases, clinical characteristics, and pathological variables affect lung cancer patients' overall survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This is a prospective survival study conducted on 100 patients with metastatic lung cancer. Metastatic sites were either intrathoracic metastases, including patients with separate tumor nodules in a contralateral lobe, pleural nodules, pleural effusion, or pericardial effusion, or extrathoracic metastases involving the liver, bone, brain, adrenal gland, or other organ. All patients were monitored regularly every 1–3 months for a minimum of 20 months. For each patient, the date of death or the last follow-up visit since diagnosis was recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e Intrathoracic metastasis and the brain were the most frequent sites of metastases, followed by the liver and bone. Patients with multiorgan metastases had significantly shorter overall survival compared with those patients with single organ metastasis. Patients with lung cancer and intrathoracic metastases have the best survival rates, while those with liver metastases have the poorest outcomes\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e. It is crucial to consider this variation in survival on metastatic sites to ensure a more tailored and effective approach when developing treatment plans for metastatic lung cancer.\u003c/p\u003e","manuscriptTitle":"The Impact of Some Clinicopathological Factors on the Overall Survival in Metastatic Lung Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 09:40:21","doi":"10.21203/rs.3.rs-9033388/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":"ae1a10d7-f589-4767-a3b6-b1ade986f863","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-18T06:56:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T13:07:30+00:00","index":73,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T00:52:13+00:00","index":72,"fulltext":""},{"type":"reviewerAgreed","content":"214988159698361339058606575089491835960","date":"2026-05-08T09:47:18+00:00","index":71,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T00:20:14+00:00","index":70,"fulltext":""},{"type":"reviewerAgreed","content":"204116608675267216547531958724166047817","date":"2026-05-07T08:12:48+00:00","index":69,"fulltext":""},{"type":"reviewerAgreed","content":"196870862902866528779650491849070038611","date":"2026-05-06T13:14:46+00:00","index":68,"fulltext":""},{"type":"reviewerAgreed","content":"112535925878800316775520379777748188983","date":"2026-05-06T12:27:29+00:00","index":67,"fulltext":""},{"type":"reviewerAgreed","content":"334266253106392329113526138987753116974","date":"2026-05-06T10:43:58+00:00","index":66,"fulltext":""},{"type":"reviewersInvited","content":"7","date":"2026-05-06T10:08:19+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":68177210,"name":"Biological sciences/Cancer"},{"id":68177211,"name":"Health sciences/Medical research"},{"id":68177212,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-05-18T07:11:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 09:40:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9033388","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9033388","identity":"rs-9033388","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}