Clinicopathological Characteristics, Prognosis, and Survival Outcomes of Advanced Stage Gastric Cancer with Single- Site Metastasis: Nationwide Real-World Data from Qatar

Clinicopathological Characteristics, Prognosis, and Survival Outcomes of Advanced Stage Gastric Cancer with Single- Site Metastasis: Nationwide Real-World Data from Qatar | 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 Research Article Clinicopathological Characteristics, Prognosis, and Survival Outcomes of Advanced Stage Gastric Cancer with Single- Site Metastasis: Nationwide Real-World Data from Qatar L.A. Zar, A. Abdalhadi, M. S. Elkhatim, S. A. Abdelrahim, N. E. Omar, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8696557/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Introduction: Although recent studies have shown a steady decline in mortality over the past several decades, Gastric cancer (GC) remains the fifth major cause of cancer-related mortality. Several prognostic factors, both patient- and tumor-related have been investigated as predictors for survival in patients with stage 4 GC. Aim : In this study, we aim to investigate whether the site of metastasis in patients newly diagnosed with stage 4 GC is a predictor for length of survival. Methods : This is a retrospective cohort study of patients treated at the National Center for Cancer Care and Research, Doha, Qatar. The data was collected between January 2015 and December 2020. We generated three groups, each including patients with metastasis to a single site: liver, peritoneum, or retroperitoneal lymph nodes (RPLN). A Kaplan-Meier survival graph was used to illustrate the overall survival of patients in the three groups. Cox proportional-hazard model was used to investigate whether site of metastasis is a predictor for overall survival. Results : A total of 134 patients with a median age of 52 (42 – 63) were diagnosed with stage IV GC. As for differentiation, around 67% had poorly differentiated GC. Of the 134 patients with Stage IV GC, 40 patients had single-site metastasis to either the liver, peritoneum, or RPLN. The Kaplan-Meier curve showed a statistically divergent increase in median overall survival (mOS) in patients with metastasis to the liver compared to peritoneum (20 vs 7, p = 0.03). Furthermore, patients with peritoneum-only metastasis had a 2.87-fold (95% UI 1.03 – 7.97, p = 0.043) increased mortality compared to liver-only metastasis. Patients with RPLN-only had similar survival compared to liver-only metastasis. Conclusion : This study shows that patients with liver-only or RPLN-only metastasis have a better mOS compared to peritoneal. As our data is from a single center, further analysis of large cohorts is needed to validate the findings. Figures Figure 1 Figure 2 Introduction The rates of Gastric cancer (GC) have been steadily declining over several decades, however, it remains the fifth leading cause of mortality among all cancers ( 1 ). The worldwide age-standardized rate of GC is 12.8% among males while in females the rate is lower (6.0%) based on a recent result from GLOBOCAN 2022( 1 ). The incidence of GC is highest in eastern Asia (224.3 per 100,000) due to the high prevalence of drug-resistant H. Pylori. A recent systematic review of GC across 11 Arab countries found that Oman had the highest age-standardized incidence of GC (8.0 per 100,000), while Qatar had a lower incidence of GC the incidence was lower (5.2 per 100,000) ( 2 ). Stage IV GC, the most advanced form of the disease, is characterized by the spread of cancer cells beyond the stomach to distant organs, such as the liver, lungs, or peritoneum ( 3 ). There is limited data from the Arab world about the clinicopathological characteristics of GC, however a recent study done in Egypt of 70 patients with confirmed GC found that the most of them were diagnosed at stage IV (55.7%) in whom the most common site of metastasis included peritoneum (53.8%), ascites (46.2%) and liver (23.1%) ( 4 ). Several demographic and pathological factors play a role in the prognosis of stage IV GC. A retrospective study conducted in Japan showed that age > 70, CA19-9, and liver metastasis were strong prognostic indicators of overall survival ( 5 ) in patients with GC. Furthermore, multiple studies have shown that patients with limited metastatic lesions have a better disease outcome compared to those with extensive metastasis( 6 , 7 ). A more recent paper found that metastasis to a single organ had better median survival compared to multi-organ metastasis in GC ( 8 ). However, despite these findings, there is limited evidence exploring whether the specific location of single-site metastasis—such as the liver, peritoneum, or lymph nodes—has a differential impact on survival outcomes in patients with stage IV GC. A retrospective population-based Swedish study found that patients with solitary bone or liver metastases experienced the worst median survival (~ 2 months), while peritoneal metastases were more frequently observed in younger patients ( 9 ). These findings point toward prognostic heterogeneity based on the metastatic site, yet the vast majority of such studies are derived from Western or East Asian populations. To date, there is a notable absence of data addressing this question in Middle Eastern populations, particularly in the Gulf region. This study addresses this critical gap by analyzing nationwide, real-world data from Qatar to characterize the clinicopathological features and survival outcomes of patients with stage IV GC and single-site metastasis. Specifically, it investigates the prevalence of metastasis to the liver, peritoneum, and RPLN, and compares overall survival among these subgroups. In doing so, it aims to determine whether the site of solitary metastasis serves as a useful prognostic factor in this population. By providing data from a Middle Eastern context, this study contributes unique regional insights that may inform future diagnostic stratification and therapeutic strategies in the management of advanced GC. Method Study Design This retrospective observational study was conducted at the National Center for Cancer Care and Research (NCCCR), the main tertiary oncology center in Doha, Qatar. The study protocol was approved by the Institutional Review Board (IRB) of Hamad Medical Corporation (MRC-01-24-522). In accordance with IRB guidelines, informed consent was waived due to the retrospective design of the study. Data were collected for all adult patients (≥18 years) with a confirmed histological diagnosis of newly diagnosed stage IV GC between January 2015 and December 2020. Patient records were identified using the institutional electronic medical records (EMR) system. Trained research personnel extracted data using a standardized data collection form. Collected variables included patient demographics (age, sex, nationality), clinical characteristics (performance status, presenting symptoms), pathological features (histological subtype, tumor location, HER2 status), and details of metastatic disease (site and number of metastases). Treatment details and survival outcomes were also recorded. To ensure data accuracy, a random subset of records was independently reviewed by a second researcher. Any discrepancies were resolved through consensus with the clinical oncology team. All patient data were de-identified prior to analysis to maintain confidentiality. Variable assessment To assess the site of metastasis for each patient, we used diagnostic imaging modalities including contrast-enhanced computed tomography (CT) and positron emission tomography (PET) scans, performed at initial staging. Imaging findings were reviewed during multidisciplinary team (MDT) meetings, where consensus was reached on the presence and location of metastatic lesions. Only patients with confirmed de novo stage IV GC and metastasis confined to a single anatomical site were included in the final analysis. Patients with evidence of multiple metastatic sites were excluded during the data-cleaning phase. The three most frequent solitary metastatic sites—liver-only, peritoneum-only, and RPLN-only—were designated as the primary exposure groups. The metastatic site was treated as a categorical variable in the analysis. The primary outcome was overall survival, defined as the time in months from the date of pathological diagnosis to the date of death or last follow-up. Statistical Analysis All analyses were conducted in Stata version 18 (10). Categorical variables were summarized using frequencies and percentages and compared using the Chi-square test or Fisher’s exact test, as appropriate. Continuous variables were reported as medians with interquartile ranges (IQRs) and compared using the Kruskal–Wallis test due to non-normal distribution. We analyzed demographic variables such as age, gender, region, and comorbidities, alongside tumor markers including CA 19-9 and CEA levels in patients diagnosed with stage IV GC. Additionally, we evaluated histological characteristics, such as differentiation level, the presence of signet-ring cells, HER2/neu status, and expression levels of PD-L1 and MMR. To address missing data, we used available case analysis, analyzing all non-missing values without imputation. For descriptive and inferential analyses, exact p-values were reported for both categorical and continuous variables. The language of statistical divergence was used in interpreting p-values rather than traditional notions of statistical significance (11). To evaluate whether the observed data diverged from a population model assuming no effect (the tested hypothesis), p-values were computed. A smaller p-value implies greater divergence of the study results from the tested hypothesis. Results with p < 0.05 were considered statistically divergent, indicating sufficient evidence to reject the tested hypothesis as a plausible explanation for the data. We also reported point estimates and their 95% uncertainty intervals (95% UI) to assess both the precision and potential practical relevance of the findings (12). The uncertainty interval represents the range of tested hypotheses under which the observed result would be expected to lie within the central 95% of the predicted distribution. A Kaplan–Meier survival analysis was conducted to compare survival duration among patients with single-site metastasis (liver-only, peritoneum-only, and retroperitoneal lymph node [RPLN]-only involvement). Differences between survival curves were evaluated using the log-rank test, with exact p-values reported. A Cox proportional hazards regression model was used to assess the association between metastatic site and overall survival. Both univariate and multivariable models were fitted, with the multivariable analysis adjusting for age and gender. Given the limited sample size (n = 40), the presence of imbalanced group sizes and rare events, we verified our result by applying the Firth penalized maximum likelihood correction. Results Patient characteristics As shown in figure 1, a total of 134 patients diagnosed with de novo Stage 4 GC were included in this study, with a median age of 52 years (IQR: 42–63). The majority of patients were male (69.4%), while 30.6% were female. In terms of geographic distribution, 55.2% of patients were from Asia, 29.9% were from the MENA region, and 15% were from other regions (Table 1). Regarding comorbid conditions, 92.5% of patients had no history of cardiovascular disease (CVD), while 7.46% had a positive CVD history (Table 1). The tumor marker levels varied among patients. The median CA19-9 level was 37.5 U/mL (IQR: 8.85–434.5), while the median carcinoembryonic antigen (CEA) level was 4.75 ng/mL (IQR: 1.9–24). The median programmed death-ligand 1 (PD-L1) expression was 5% (IQR: 0–20%). Mismatch repair (MMR) status was negative in 94.8% of patients, while only 5.13% had positive MMR status. Tumor differentiation was predominantly poor, observed in 67.2% of patients, while moderate to poor differentiation was noted in 1.7%. Signet-ring cell carcinoma was positive in 35.9% of cases. Human epidermal growth factor receptor 2 (HER2) status was negative in 83.6% of patients, with 16.4% testing positive. The median overall survival for the cohort was 11 months (IQR: 8–15), with a mean survival time of 8.9 months (SD: 10.8). Regarding the location of the primary tumor, the most common sites were the body of the stomach (49.3%), followed by the antrum (21.6%), pylorus (2.99%), and other regions (26.1%). Metastasis was observed at multiple sites. The most common metastatic sites were the liver (48 patients), peritoneum (59 patients), RPLN (54 patients), and lung or pleural effusion (16 patients). Other metastatic sites included the adrenal glands, brain, omentum, and bone. Table 1. Baseline Characteristics, Diagnostic Markers, and Survival Outcomes of Patients diagnosed with Stage IV Gastric Cancer Variables Total population means (N = 134) Median (iqr) Age 52.4 (13.7) 52 (42 – 63 ) Gender Male 93 (69.4%) Female 41 (30.6%) Region Asia 74 (55.2%) MENA 40 (29.9%) Other 20 (15%) CVD No 124 (92.5%) Yes 10 (7.46 %) HTN No 95 (70.9%) Yes 39 (26.1%) DM No 97 (72.4%) Yes 37 (27.6%) CA19-9 1264.4 (2976.2) 37.5 (8.85 – 434.5) CEA 166.2 (916.7) 4.75 (1.9 – 24 ) PD-L1 13.1 (19.2) 5 (0 – 20) MMR Negative 74 (94.8%) Positive 4 (5.13%) Differentiation Moderate 26 (22.4%) Moderate to poor 2 (1.7%) Poor 78 (67.2%) N/A 10 (8.6%) Signet-ring Negative 86 (64.2%) Positive 48 (35.8%) HER2 Negative 107 (83.6%) Positive 21 (16.4%) Overall median survival Months, (95% UI) 11 (8 – 15) Malignant lesion site Body 66 (49.3%) Pylorus 4 (2.99%) Antrum 29 (21.6%) Other 35 (26.1%) Site of metastasis Liver 48 Peritoneum 59 Omentum 31 RPLN 54 Lung/Pleural Effusion 16 Bone 16 Adrenal 5 Ovary 7 Brain 2 Single-site metastasis results Only 40 patients were identified as having a single- site of metastasis distribute as follows; liver (n=16), peritoneum (n=15), and RPLN(n=9) (Figure 1). Table 2 compares the baseline characteristics of these patients. Patients with liver metastasis had a higher median age of 64.0 years (IQR: 54.5–68.0), while those with peritoneal metastasis were younger, with a median age of 46.0 years (IQR: 40.0–57.0). The RPLN group had a median age of 57.0 years (IQR: 43.0–73.0). The liver metastasis group had a higher proportion of males (94%), while the peritoneum and RPLN groups had a lower male prevalence (47% and 78%, respectively). Among tumor markers, median CA19-9 levels were highest in the peritoneum group at 36.8 U/mL (IQR: 14.8–94.0), followed by the RPLN group at 32.0 U/mL (IQR: 23.0–7730.0) (p = 0.32), and liver group at 10.3 U/mL (IQR: 5.0–7683.0). Median CEA levels differed between the groups, showing statistical divergence (p = 0.043), with the highest levels in the liver metastasis group (13.5 ng/mL, IQR: 2.0–159.0), compared to the RPLN (2.6 ng/mL, IQR: 1.4–21.1) and peritoneum groups (1.6 ng/mL, IQR: 1.1–2.0). Tumor differentiation was predominantly poor in all groups, with 64% of patients in the total population exhibiting poor differentiation. The RPLN group had the highest percentage of poor differentiation (71%), followed by the peritoneum group (73%) and liver group (50%) (p = 0.40). Signet-ring cell carcinoma was present in 32% of the total population, with the highest prevalence in the liver group (100%) and lower rates in the peritoneum (47%) and RPLN groups (44%) (p = 0.002). HER2 positivity was similar across groups, with no statistically divergent differences (p = 0.18). PD-L1 positivity varied slightly, with the highest levels in the liver group (median 5%, IQR: 1.1–10.0) compared to the RPLN group (median 10%, IQR: 5.0–10.0) and the peritoneum group (median 2%, IQR: 0.0–3.0) (p = 0.10). MMR deficiency was rare across all groups, indicating non-divergence (p = 0.49). The liver metastasis group had the highest percentage of patients treated for cancer (29%), while the RPLN group had the highest percentage of untreated patients (56%) (p = 0.40). The most common location of primary gastric lesions was the body of the stomach (60%), with statistically non-divergent differences in location distribution across groups (p = 0.71). Table 2. Comparison of Characteristics of Patients with Liver-only, Peritoneum-only, and RPLN-only metastasis Total Liver Peritoneum RPLN p-value N=40 N=16 N=15 N=9 Age Median (iqr) 57.0 (43.5-66.0) 64.0 (54.5-68.0) 46.0 (40.0-57.0) 57.0 (43.0-73.0) 0.074 Gender Male 29 (72%) 15 (94%) 7 (47%) 7 (78%) 0.012 Female 11 (28%) 1 ( 6%) 8 (53%) 2 (22%) Region Asian 19 (48%) 8 (50%) 8 (53%) 3 (33%) 0.36 Arab 16 (40%) 8 (50%) 5 (33%) 3 (33%) Others 5 ( 13%) 0 ( 0%) 2 (14%) 3 (33%) CVD No 35 (88%) 14 (88%) 12 (80%) 9 (100%) 0.36 Yes 5 (12%) 2 (12%) 3 (20%) 0 ( 0%) HTN No 26 (65%) 11 (69%) 10 (67%) 5 (56%) 0.79 Yes 14 (35%) 5 (31%) 5 (33%) 4 (44%) DM No 26 (65%) 9 (56%) 11 (73%) 6 (67%) 0.60 Yes 14 (35%) 7 (44%) 4 (27%) 3 (33%) COPD/asthma No 35 (88%) 14 (88%) 14 (93%) 7 (78%) 0.54 Yes 5 (12%) 2 (12%) 1 ( 7%) 2 (22%) CA19-9 Median (iqr) 23.0 (10.3-393.0) 10.3 (5.0-7683.0) 36.8 (14.8-94.0) 32.0 (23.0-7730.0) 0.32 CEA Median (iqr) 2.1 (1.4-13.5) 13.5 (2.0-159.0) 1.6 (1.1-2.0) 2.6 (1.4-21.1) 0.043 Differentiation moderate 10 (28%) 6 (43%) 2 (13%) 2 (29%) 0.29 poor 23 (64%) 7 (50%) 11 (73%) 5 (71%) 0.25 N/A 3 ( 8%) 1 ( 7%) 2 (13%) 0 ( 0%) Signet-ring No 27 (68%) 16 (100%) 7 (47%) 4 (44%) 0.002 Yes 13 (32%) 0 ( 0%) 8 (53%) 5 (56%) HER2 No 31 (79%) 11 (69%) 11 (79%) 9 (100%) 0.18 Yes 8 (21%) 5 (31%) 3 (21%) 0 ( 0%) PDL1 +ve Median (iqr) 4.0 (1.6-10.0) 5.0 (1.1-10.0) 2.0 (0.0-3.0) 10.0 (5.0-10.0) 0.10 MMR No 20 (91%) 7 (100%) 9 (90%) 4 (80%) 0.49 Yes 2 ( 9%) 0 ( 0%) 1 (10%) 1 (20%) Treated No 14 (37%) 4 (29%) 5 (33%) 5 (56%) 0.40 Yes 24 (63%) 10 (71%) 10 (67%) 4 (44%) Location of primary lesion Lower gastric 11 (28%) 4 (25%) 5 (33%) 2 (22%) 0.81 Middle gastric 18 (45%) 6 (38%) 9 (60%) 3 (33%) 0.33 Upper gastric 10 (25%) 5 (31%) 1 (7%) 4 (44%) 0.089 Survival Analysis Results Kaplan–Meier analysis demonstrated a median overall survival (OS) of 20.7 months in patients with liver-only metastasis, compared to 7.0 months in those with peritoneum-only metastasis and 18.0 months in those with RPLN-only metastasis (Figure 2). In univariate Cox regression analysis, peritoneum-only metastasis showed statistical divergence compared to liver-only metastasis (HR = 2.87, 95% UI: 1.03–7.97, p = 0.04), (Table 3). In contrast, RPLN-only metastasis did not demonstrate statistical divergence (HR = 1.07, 95% UI: 0.32–3.64, p = 0.90). After adjusting for age and gender, the association between peritoneum-only metastasis and reduced survival was not statistically divergent (adjusted HR = 2.9, 95% UI: 0.67–12.69, p = 0.15), and RPLN-only metastasis remained non-divergent (adjusted HR = 1.22, 95% UI: 0.35–4.19, p = 0.75). The wide uncertainty intervals, particularly in the multivariable analysis, reflect a high degree of imprecision, likely due to small subgroup sizes. Intervals that include the null value (HR = 1.0) suggest that the observed effects are also compatible with minimal or no difference in survival (Table 3). In the Firth-penalized Cox regression model, the site of metastasis was associated with differential overall survival (Table 4). Using liver metastasis as the reference category, patients with peritoneal metastasis demonstrated an increased risk of death (HR = 2.81, 95% UI: 1.05–7.85, p = 0.04). In contrast, patients with RPLN metastasis did not exhibit a statistically divergent difference in hazard compared to those with liver metastases (HR = 1.14, 95% UI: 0.32–3.51, p = 0.83). These results suggest that peritoneal metastasis may be associated with a worse prognosis relative to liver involvement, while RPLN metastasis appears to confer a similar risk profile. Table 3. Univariate and Multivariable Cox-proportional regression analysis comparing single-site metastasis Site Univariate HR (95% UI)* p-value Multivariable HR (95%UI) p-value Peritoneum 2.87 (1.03 – 7.97) 0.04 2.9 (0.67–12.69) 0.15 RPLN 1.07 (0.32 – 3.64) 0.90 1.22 (0.35–4.19) 0.75 * Compared to liver metastasis Table 4. Firth-penalized Cox-proportional regression analysis comparing single-site metastasis Site HR (95% UI) * p-value Peritoneum 2.81 (1.05 – 7.85) 0.04 RPLN 1.14 (0.32 – 3.51) 0.83 *Compared to liver metastasis Discussion To the best of our knowledge, this is the first study from the MENA region to examine the clinicopathological characteristics, prognosis, and survival outcomes of advanced-stage gastric cancer with single-site metastasis using real-world data from Qatar. Unlike previous studies, our cohort includes a diverse population comprising individuals from Asian, Middle Eastern Arab, and African backgrounds, offering broader regional insight into metastatic patterns and outcomes. In this study, we analyzed the prognostic outcomes of patients diagnosed with stage IV GC, with a specific focus on those who had single-site of metastasis. Based on our data, liver, peritoneum, and RPLN were the most common sites of metastasis. In the overall sample of patients with GC, the most common site of metastasis was the peritoneum. This is consistent with recent results from a nationwide cancer registry in the Netherlands, which found that 58% of patients with gastric cancer–related peritoneal metastasis had isolated peritoneal involvement ( 13 ). In comparison, a 2016 population-based study from Sweden found liver metastasis to be the most common site followed by peritoneum and lung ( 9 ). The reason for this variation may be due to the difference in patient demographic including race, age distribution, and genetic factors ( 14 – 17 ). The liver-only metastasis group had a higher prevalence of male patients, and older median age compared to those with peritoneum or RPLN metastasis. This is consistent with a previous study suggesting that liver-only metastasis in GC patients tends to occur in older populations ( 18 ). Additionally, our results show that liver-only metastasis is associated with a favorable prognosis compared to RPLN and peritoneum-only metastasis. Furthermore, studies have shown that GC patients with liver-only metastasis who undergo gastrectomy and/or hepatectomy have further improvement in overall survival ( 19 , 20 ). However, only two patients in our cohort received surgical intervention, highlighting a potential underutilization of surgery in this subgroup. Future clinical practice should consider selecting appropriate patients with liver-only metastasis for surgical management to potentially enhance survival outcomes. Our results are consistent with studies utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, which included patients with metastatic GC, found that patients with liver or lung metastasis exhibited better survival( 21 ). However, a more recent study conducted by Wang et al. using the SEER database found that liver metastasis was an adverse prognostic factor for OS. Additionally, their multivariable Cox proportional hazard ration revealed that patients with liver metastasis had a much worse survival compared to lung-only( 22 ). Although we did not compare liver-only metastasis to other sites such as lung, we found that liver-only metastasis had better OS in the overall population. A more recent 2024 retrospective study based on SEER database found liver metastasis to be the most common single organ metastasis, and bone metastasis leading to the worst OS ( 23 ). Within our sample, we found that peritonea-only metastasis had the worst OS compared to both liver-only and RPLN-only metastasis. In a Dutch registry (2015–2020), patients with isolated peritoneal metastases had a median OS of only 4.4 months, nearly identical to those with isolated non-peritoneal metastases (4.6 months), with an adjusted HR ≈ 0.94 (p = 0.185) ( 13 ). A systematic review found that the median OS for gastric peritoneal metastases ranged from 2–9 months( 24 ). Furthermore, our study shows that patients with signet-ring cell positive are at a higher risk of peritoneal metastasis which is consistent with previous studies ( 9 , 19 , 25 ). Additionally, our results suggest that tumor markers such as CA19-9, CEA, and PD-L1 expression vary depending on the site of metastasis. Specifically, CA19-9 levels were higher in patients with RPLN-only and peritoneum-only metastasis compared to liver-only metastasis ( 26 ). Previous studies have shown it to be strongly associated with lymph-node, peritoneal ,and serosal involvement ( 27 , 28 ). Elevated tumor markers predict peritoneal disease. In a series of advanced GC patients, 80.6% of those with CA125 ≥ 35 U/mL had peritoneal metastasis, and high CA125 was associated with shorter survival ( 29 ). Recent studies have shown that combining CEA, CA19-9, and CA72-4 may help in improving the prognostic value compared with using a single tumor marker ( 30 ). Notably, a recent study found that nearly one-third of HER2-negative primary tumors converted to HER2-low in metastatic lesions, particularly in metachronous liver and lung metastases ( 31 ). This evolution has important clinical implications, as it could expand eligibility for HER2-targeted antibody-drug conjugate (ADC) therapies, such as trastuzumab deruxtecan, which have shown efficacy in HER2-low expressing tumors. Therefore, re-evaluating HER2 status in metastatic lesions, especially in non-peritoneal sites like the liver, is crucial when considering systemic treatment strategies. Our study has several limitations, including the retrospective nature of the data and the small sample size, particularly in subgroup analyses. These factors may introduce bias and limit the generalizability of our findings. Nevertheless, the study offers several notable strengths. Importantly, despite the limited sample size (N = 40), we observed a statistically divergent association between peritoneum-only metastasis and worse overall survival compared to liver-only metastasis in both Kaplan-Meier and univariate Cox regression analyses. However, multivariable models had wider uncertainty intervals, reflecting reduced statistical power and the need for cautious interpretation. Further large cohort studies are needed to examine how combined molecular markers, and metastatic patterns influence prognosis in advanced-stage gastric cancer. In addition, future research should explore how metastatic patterns can inform a more individualized, patient-centered approach to treatment selection. Abbreviations GC: Gastric cancer OS: Overall survival mOS: Median overall survival RPLN: Retroperitoneal lymph nodes IRB: Institutional Review Board NCCCR: National Center for Cancer Care and Research HMC: Hamad Medical Corporation CT: Computed tomography PET: Positron emission tomography MMR: Mismatch repair PD-L1: Programmed death-ligand 1 HER2: Human epidermal growth factor receptor 2 CEA: Carcinoembryonic antigen CA19-9: Carbohydrate antigen 19-9 Declarations Data Availability statement The datasets generated and/or analysed during the current study are not publicly available due to ethical and institutional restrictions related to patient confidentiality but are available from the corresponding author on reasonable request. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding Statement The authors declare that this study received no external funding. Author Contribution Statement (CRediT) Conceptualization was carried out by A.S., A.A., K.R., and S.B. Methodology development and formal analysis were performed by L.A.Z., A.S., and N.E.O. Data curation and investigation were handled by M.S.E., S.A.A., M.M., E.T., A.A., A.S., and K.R. Visualization was prepared by L.A.Z., A.S., and N.E.O. Resources and project administration were provided by A.S., K.R., S.B., W.A., R.A., A.J., and M.M. Supervision of the study was conducted by S.A., M.S.E., S.A.A., A.J., R.A., W.A., A.A., and M.M. The original draft of the manuscript was written by L.A.Z., A.A., A.S., and N.E.O., and all authors contributed to the review and editing of the final manuscript. All authors read and approved the final version of the manuscript. Ethics and Informed Consent Statement The study protocol was approved by the Institutional Review Board (IRB) of Hamad Medical Corporation (MRC-01-24-522). The study was conducted in accordance with the principles of the Declaration of Helsinki. In accordance with IRB guidelines, informed consent was waived due to the retrospective design of the study. Consent for publication Not applicable. Acknowledgements The authors would like to thank the National Center for Cancer Care and Research at Hamad Medical Corporation for providing access to clinical data and institutional support. We also acknowledge the multidisciplinary oncology teams involved in the care of the patients included in this study. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. Aoude M, Mousallem M, Abdo M, Youssef B, Kourie HR, Al-Shamsi HO. Gastric cancer in the Arab World: a systematic review. East Mediterr Health J. 2022 Jul 30;28(7):521–31. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet Lond Engl. 2020 Aug 29;396(10251):635–48. Alorabi MO, El-Bassiouny M, Khodary DAEGE, Din MMAEE, Elsayed AMMA, Reda C. Clinical presentation and treatment outcomes of gastric adenocarcinoma patients: a retrospective study from Ain Shams Clinical Oncology Department [Internet]. 2025 [cited 2025 May 30]. Available from: http://ecancer.org/en/journal/article/1861-clinical-presentation-and-treatment-outcomes-of-gastric-adenocarcinoma-patients-a-retrospective-study-from-ain-shams-clinical-oncology-department Baba H, Kuwabara K, Ishiguro T, Kumamoto K, Kumagai Y, Ishibashi K, et al. Prognostic Factors for Stage IV Gastric Cancer. Int Surg. 2013;98(2):181–7. Salati M, Valeri N, Spallanzani A, Braconi C, Cascinu S. Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications. Eur J Surg Oncol. 2019 Aug 1;45(8):1479–82. Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, et al. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237–44. Zhan PL, Canavan ME, Ermer T, Pichert MD, Li AX, Maduka RC, et al. Association Between Metastatic Pattern and Prognosis in Stage IV Gastric Cancer: Potential for Stage Classification Reform. Ann Surg Oncol. 2023 Jul 1;30(7):4180–91. Riihimäki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K. Metastatic spread in patients with gastric cancer. Oncotarget. 2016 Jul 20;7(32):52307–16. StataCorp. College Station, TX; 2023. (Stata Statistical Software). Zar LA, Abdulmajeed J, Elshoeibi AM, Syed A, Awaisu A, Glasziou P, et al. From significance to divergence: guiding statistical interpretation through language. Curr Opin Epidemiol Public Health. :10.1097/PXH.0000000000000050. Gelman A, Greenland S. Are confidence intervals better termed “uncertainty intervals”? 2019 Sep 10 [cited 2025 Jun 8]; Available from: https://www.bmj.com/content/366/bmj.l5381 Guchelaar NAD, de Neijs MJ, Noordman BJ, Graaf HEC, van Hellemond IEG, van der Sluis PC, et al. The prognostic value of peritoneal metastases in patients with gastric cancer: a nationwide population-based study. EClinicalMedicine. 2025 Mar;81:103109. Tseng JF, Mansfield PF, Feig BW, Pisters PW, Ajani JA, Yao JC. The effect of ethnicity on presentation, pattern of metastasis, and survival in gastric adenocarcinoma at a single center. J Clin Oncol. 2004 Jul 15;22(14_suppl):4016–4016. Klapheke AK, Carvajal-Carmona LG, Cress RD. Racial/Ethnic Differences in Survival among Gastric Cancer Patients in California: Gastric Cancer Survival by Race. Cancer Causes Control CCC. 2019 Jul;30(7):687–96. Gonzalez‐Pons M, Torres‐Cintrón CR, Soto‐Salgado M, Vargas‐Ramos Y, Perez‐Portocarrero L, Morgan DR, et al. Racial/ethnic disparities in gastric cancer: A 15‐year population‐based analysis. Cancer Med. 2022 Jul 3;12(2):1860–8. El Halabi M, Horanieh R, Tamim H, Mukherji D, Jdiaa S, Temraz S, et al. The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre. J Gastrointest Oncol. 2020 Dec;11(6):1233–41. Zhang H, Cheng X, Guo W, Zheng C, Zhang Y, Jing X, et al. Metastasis patterns and prognosis in young gastric cancer patients: A propensity score‑matched SEER database analysis. PLOS ONE. 2024 Apr 9;19(4):e0301834. Sun W, Li X. Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population‐Based, Case‐Control Study. Health Sci Rep. 2024 Dec 12;7(12):e70220. Takahashi K, Terashima M, Notsu A, Koseki Y, Furukawa K, Fujiya K, et al. Surgical treatment for liver metastasis from gastric cancer: A systematic review and meta-analysis of long-term outcomes and prognostic factors. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2024 Oct;50(10):108582. Li Y, Xie D, Chen X, Hu T, Lu S, Han Y. Prognostic Value of the Site of Distant Metastasis and Surgical Interventions in Metastatic Gastric Cancer: A Population-Based Study. Technol Cancer Res Treat. 2020;19:1533033820964131. Wang J, Li S, Liu Y, Zhang C, Li H, Lai B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population‐based analysis. Cancer Med. 2019 Nov 6;9(1):361–73. Zhao QW, Quan Z, Liu SS, Wang YD, Guo HN. Heterogeneity and prognosis of single organ metastases in gastric cancer. Transl Gastroenterol Hepatol. 2024 Sep 25;9:61. Rijken A, Lurvink RJ, Luyer MDP, Nieuwenhuijzen GAP, van Erning FN, van Sandick JW, et al. The Burden of Peritoneal Metastases from Gastric Cancer: A Systematic Review on the Incidence, Risk Factors and Survival. J Clin Med. 2021 Oct 23;10(21):4882. Thomassen I, van Gestel YR, van Ramshorst B, Luyer MD, Bosscha K, Nienhuijs SW, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014 Feb 1;134(3):622–8. Hasbahceci M, Malya F, Kunduz E, Guler M, Unver N, Akcakaya A. Use of serum and peritoneal CEA and CA19-9 in prediction of peritoneal dissemination and survival of gastric adenocarcinoma patients: are they prognostic factors? Ann R Coll Surg Engl. 2018 Apr;100(4):257–66. Ucar E, Semerci E, Ustun H, Yetim T, Huzmeli C, Gullu M. Prognostic value of preoperative CEA, CA 19-9, CA 72-4, and AFP levels in gastric cancer. Adv Ther. 2008 Oct;25(10):1075–84. Yamamoto M, Baba H, Toh Y, Okamura T, Maehara Y. Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients. J Cancer Res Clin Oncol. 2007 Jul;133(7):471–6. Ueda A, Yuki S, Ando T, Hosokawa A, Nakada N, Kito Y, et al. CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer. Cancers. 2024 Jan;16(5):871. Zhang R, Chen X, Chen G, Zhao Z, Wei Y, Zhang F, et al. Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality. Ann Surg Oncol. 2023 Dec;30(13):8561–71. He WZ, Yang YZ, Yin CX, Xian XY, Gu JM, Yi JH, et al. Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions. Npj Precis Oncol. 2025 Apr 15;9(1):1–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Mar, 2026 Reviewers agreed at journal 08 Mar, 2026 Reviews received at journal 06 Mar, 2026 Reviewers agreed at journal 06 Mar, 2026 Reviewers invited by journal 05 Mar, 2026 Editor assigned by journal 05 Mar, 2026 Editor invited by journal 06 Feb, 2026 Submission checks completed at journal 06 Feb, 2026 First submitted to journal 06 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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-8696557","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":602966897,"identity":"4cd590b3-5cc1-4fb5-b841-15ec6df983b0","order_by":0,"name":"L.A. Zar","email":"","orcid":"","institution":"Qatar University","correspondingAuthor":false,"prefix":"","firstName":"L.A.","middleName":"","lastName":"Zar","suffix":""},{"id":602966899,"identity":"ada56f0a-4731-40d5-a70f-3ae96805e251","order_by":1,"name":"A. Abdalhadi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIie3OQQsBQRjG8dHW7GWW625r8xVGakvCV6EpLkuOysGenBZn32JP40pvcVGulOK0p1VOoiij3JTBSZr/8a1fz4uQSvWDYY0gE7UmCIE2ux8Svoyk9EAQeie49h6xgsWDTIj7HqGrxnR1optMck6Ou7NXcnyd7SSkyfIBjbIjMMbZPmc5n0RUQjzXJBQSIRjcNLhW9c3Ka1Lexq51oVAOgUTWlXcFqR+kK7ZYqQqCbYODIJ7ssSYrpCmwEWDXdvg81yNxS0Ia03XchuJgCZG15x1nqNfDl+Q5jCofCtEXRKVSqf66GzWSUN7bRZEhAAAAAElFTkSuQmCC","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":true,"prefix":"","firstName":"A.","middleName":"","lastName":"Abdalhadi","suffix":""},{"id":602966900,"identity":"5ece5442-06a8-47c1-a881-b3a2f0c10298","order_by":2,"name":"M. S. Elkhatim","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"S.","lastName":"Elkhatim","suffix":""},{"id":602966901,"identity":"2a2c6819-92fd-465e-adb2-58ae60c0d6de","order_by":3,"name":"S. A. Abdelrahim","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"A.","lastName":"Abdelrahim","suffix":""},{"id":602966904,"identity":"1d7a4acf-cd66-4a3c-bb1f-17aaea8959de","order_by":4,"name":"N. E. Omar","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"N.","middleName":"E.","lastName":"Omar","suffix":""},{"id":602966906,"identity":"0d6a6049-8040-491e-9bb2-95f5eddc0337","order_by":5,"name":"S. Abdo","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Abdo","suffix":""},{"id":602966907,"identity":"b765f1dc-9084-4541-bf43-a9fc5451e571","order_by":6,"name":"A. Jama","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"","lastName":"Jama","suffix":""},{"id":602966909,"identity":"c6569bee-06de-4df6-9dbd-23806a3a4e5f","order_by":7,"name":"R. Anil","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"R.","middleName":"","lastName":"Anil","suffix":""},{"id":602966910,"identity":"c5a4fc55-fad1-495a-8773-eab2998f6b98","order_by":8,"name":"W. Abdalla","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"W.","middleName":"","lastName":"Abdalla","suffix":""},{"id":602966911,"identity":"4eae76e2-aec4-480d-9295-fe400c7b58d1","order_by":9,"name":"A. Akram","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"","lastName":"Akram","suffix":""},{"id":602966913,"identity":"63bc4737-b143-4fbf-9927-0c5fd595fefd","order_by":10,"name":"M. Mostafa","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"","lastName":"Mostafa","suffix":""},{"id":602966916,"identity":"1da22ba3-2300-4b9f-a8c9-87e04bcbd72f","order_by":11,"name":"E. Tubishat","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"E.","middleName":"","lastName":"Tubishat","suffix":""},{"id":602966918,"identity":"ae4ded03-8f89-419a-accd-2be7fc0073ee","order_by":12,"name":"S. Bujassoum","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Bujassoum","suffix":""},{"id":602966919,"identity":"ce114472-437d-486a-9fdc-49db8d5bfd65","order_by":13,"name":"K. Rasul","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"K.","middleName":"","lastName":"Rasul","suffix":""},{"id":602966921,"identity":"52c25a0f-09da-4c1b-88e6-b65dd9afa855","order_by":14,"name":"A. Shablak","email":"","orcid":"","institution":"Hamad Medical Corporation","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"","lastName":"Shablak","suffix":""}],"badges":[],"createdAt":"2026-01-26 04:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8696557/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8696557/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104470634,"identity":"0e8db9a4-6e5a-4d6b-a686-e7869c320bc9","added_by":"auto","created_at":"2026-03-12 07:22:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58210,"visible":true,"origin":"","legend":"\u003cp\u003eA flow diagram demonstrating patient selection and group allocation\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8696557/v1/ea51fe4988b95251d3b8aacc.png"},{"id":104470636,"identity":"e864406b-950f-4d20-ba40-5d516f5d02ea","added_by":"auto","created_at":"2026-03-12 07:22:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122757,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival\u003cstrong\u003e \u003c/strong\u003egraph shows the overall survival (OS) in the three single-site of metastases groups of patients with stage IV GC\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8696557/v1/a03515800a5b36b72c160639.png"},{"id":104780435,"identity":"1cc3726b-800f-4231-9c01-0989e02f34db","added_by":"auto","created_at":"2026-03-17 07:52:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1028001,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8696557/v1/b1812894-420c-4d0c-ad1c-d5e137dcfcc2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinicopathological Characteristics, Prognosis, and Survival Outcomes of Advanced Stage Gastric Cancer with Single- Site Metastasis: Nationwide Real-World Data from Qatar","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe rates of Gastric cancer (GC) have been steadily declining over several decades, however, it remains the fifth leading cause of mortality among all cancers (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The worldwide age-standardized rate of GC is 12.8% among males while in females the rate is lower (6.0%) based on a recent result from GLOBOCAN 2022(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The incidence of GC is highest in eastern Asia (224.3 per 100,000) due to the high prevalence of drug-resistant \u003cem\u003eH. Pylori.\u003c/em\u003e A recent systematic review of GC across 11 Arab countries found that Oman had the highest age-standardized incidence of GC (8.0 per 100,000), while Qatar had a lower incidence of GC the incidence was lower (5.2 per 100,000) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Stage IV GC, the most advanced form of the disease, is characterized by the spread of cancer cells beyond the stomach to distant organs, such as the liver, lungs, or peritoneum (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). There is limited data from the Arab world about the clinicopathological characteristics of GC, however a recent study done in Egypt of 70 patients with confirmed GC found that the most of them were diagnosed at stage IV (55.7%) in whom the most common site of metastasis included peritoneum (53.8%), ascites (46.2%) and liver (23.1%) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral demographic and pathological factors play a role in the prognosis of stage IV GC. A retrospective study conducted in Japan showed that age\u0026thinsp;\u0026gt;\u0026thinsp;70, CA19-9, and liver metastasis were strong prognostic indicators of overall survival (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) in patients with GC. Furthermore, multiple studies have shown that patients with limited metastatic lesions have a better disease outcome compared to those with extensive metastasis(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A more recent paper found that metastasis to a single organ had better median survival compared to multi-organ metastasis in GC (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, despite these findings, there is limited evidence exploring whether the specific location of single-site metastasis\u0026mdash;such as the liver, peritoneum, or lymph nodes\u0026mdash;has a differential impact on survival outcomes in patients with stage IV GC. A retrospective population-based Swedish study found that patients with solitary bone or liver metastases experienced the worst median survival (~\u0026thinsp;2 months), while peritoneal metastases were more frequently observed in younger patients (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). These findings point toward prognostic heterogeneity based on the metastatic site, yet the vast majority of such studies are derived from Western or East Asian populations. To date, there is a notable absence of data addressing this question in Middle Eastern populations, particularly in the Gulf region.\u003c/p\u003e \u003cp\u003eThis study addresses this critical gap by analyzing nationwide, real-world data from Qatar to characterize the clinicopathological features and survival outcomes of patients with stage IV GC and single-site metastasis. Specifically, it investigates the prevalence of metastasis to the liver, peritoneum, and RPLN, and compares overall survival among these subgroups. In doing so, it aims to determine whether the site of solitary metastasis serves as a useful prognostic factor in this population. By providing data from a Middle Eastern context, this study contributes unique regional insights that may inform future diagnostic stratification and therapeutic strategies in the management of advanced GC.\u003c/p\u003e"},{"header":"Method","content":"\u003ch2\u003eStudy Design \u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis retrospective observational study was conducted at the National Center for Cancer Care and Research (NCCCR), the main tertiary oncology center in Doha, Qatar. The study protocol was approved by the Institutional Review Board (IRB) of Hamad Medical Corporation (MRC-01-24-522). In accordance with IRB guidelines, informed consent was waived due to the retrospective design of the study.\u003c/p\u003e\n\u003cp\u003eData were collected for all adult patients (\u0026ge;18 years) with a confirmed histological diagnosis of newly diagnosed stage IV GC between January 2015 and December 2020. Patient records were identified using the institutional electronic medical records (EMR) system. Trained research personnel extracted data using a standardized data collection form. Collected variables included patient demographics (age, sex, nationality), clinical characteristics (performance status, presenting symptoms), pathological features (histological subtype, tumor location, HER2 status), and details of metastatic disease (site and number of metastases). Treatment details and survival outcomes were also recorded.\u003c/p\u003e\n\u003cp\u003eTo ensure data accuracy, a random subset of records was independently reviewed by a second researcher. Any discrepancies were resolved through consensus with the clinical oncology team. All patient data were de-identified prior to analysis to maintain confidentiality.\u003c/p\u003e\n\u003ch2\u003eVariable assessment\u003c/h2\u003e\n\u003cp\u003eTo assess the site of metastasis for each patient, we used diagnostic imaging modalities including contrast-enhanced computed tomography (CT) and positron emission tomography (PET) scans, performed at initial staging. Imaging findings were reviewed during multidisciplinary team (MDT) meetings, where consensus was reached on the presence and location of metastatic lesions. Only patients with confirmed de novo stage IV GC and metastasis confined to a single anatomical site were included in the final analysis. Patients with evidence of multiple metastatic sites were excluded during the data-cleaning phase.\u003c/p\u003e\n\u003cp\u003eThe three most frequent solitary metastatic sites\u0026mdash;liver-only, peritoneum-only, and RPLN-only\u0026mdash;were designated as the primary exposure groups. The metastatic site was treated as a categorical variable in the analysis. The primary outcome was overall survival, defined as the time in months from the date of pathological diagnosis to the date of death or last follow-up.\u003c/p\u003e\n\u003ch2\u003eStatistical Analysis\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAll analyses were conducted in Stata version 18 (10). Categorical variables were summarized using frequencies and percentages and compared using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Continuous variables were reported as medians with interquartile ranges (IQRs) and compared using the Kruskal\u0026ndash;Wallis test due to non-normal distribution. We analyzed demographic variables such as age, gender, region, and comorbidities, alongside tumor markers including CA 19-9 and CEA levels in patients diagnosed with stage IV GC. Additionally, we evaluated histological characteristics, such as differentiation level, the presence of signet-ring cells, HER2/neu status, and expression levels of PD-L1 and MMR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo address missing data, we used available case analysis, analyzing all non-missing values without imputation. For descriptive and inferential analyses, exact p-values were reported for both categorical and continuous variables. The language of statistical divergence was used in interpreting p-values rather than traditional notions of statistical significance (11). To evaluate whether the observed data diverged from a population model assuming no effect (the tested hypothesis), p-values were computed. A smaller p-value implies greater divergence of the study results from the tested hypothesis. Results with p \u0026lt; 0.05 were considered statistically divergent, indicating sufficient evidence to reject the tested hypothesis as a plausible explanation for the data.\u003c/p\u003e\n\u003cp\u003eWe also reported point estimates and their 95% uncertainty intervals (95% UI) to assess both the precision and potential practical relevance of the findings (12). The uncertainty interval represents the range of tested hypotheses under which the observed result would be expected to lie within the central 95% of the predicted distribution.\u003c/p\u003e\n\u003cp\u003eA Kaplan\u0026ndash;Meier survival analysis was conducted to compare survival duration among patients with single-site metastasis (liver-only, peritoneum-only, and retroperitoneal lymph node [RPLN]-only involvement). Differences between survival curves were evaluated using the log-rank test, with exact p-values reported. A Cox proportional hazards regression model was used to assess the association between metastatic site and overall survival. Both univariate and multivariable models were fitted, with the multivariable analysis adjusting for age and gender. Given the limited sample size (n = 40), the presence of imbalanced group sizes and rare events, we verified our result by applying the Firth penalized maximum likelihood correction.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003ePatient characteristics\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAs shown in figure 1, a total of 134 patients diagnosed with de novo Stage 4 GC were included in this study, with a median age of 52 years (IQR: 42\u0026ndash;63). The majority of patients were male (69.4%), while 30.6% were female. In terms of geographic distribution, 55.2% of patients were from Asia, 29.9% were from the MENA region, and 15% were from other regions (Table 1). Regarding comorbid conditions, 92.5% of patients had no history of cardiovascular disease (CVD), while 7.46% had a positive CVD history (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe tumor marker levels varied among patients. The median CA19-9 level was 37.5 U/mL (IQR: 8.85\u0026ndash;434.5), while the median carcinoembryonic antigen (CEA) level was 4.75 ng/mL (IQR: 1.9\u0026ndash;24). The median programmed death-ligand 1 (PD-L1) expression was 5% (IQR: 0\u0026ndash;20%). Mismatch repair (MMR) status was negative in 94.8% of patients, while only 5.13% had positive MMR status. Tumor differentiation was predominantly poor, observed in 67.2% of patients, while moderate to poor differentiation was noted in 1.7%. Signet-ring cell carcinoma was positive in 35.9% of cases. Human epidermal growth factor receptor 2 (HER2) status was negative in 83.6% of patients, with 16.4% testing positive.\u003c/p\u003e\n\u003cp\u003eThe median overall survival for the cohort was 11 months (IQR: 8\u0026ndash;15), with a mean survival time of 8.9 months (SD: 10.8). Regarding the location of the primary tumor, the most common sites were the body of the stomach (49.3%), followed by the antrum (21.6%), pylorus (2.99%), and other regions (26.1%). Metastasis was observed at multiple sites. The most common metastatic sites were the liver (48 patients), peritoneum (59 patients), RPLN (54 patients), and lung or pleural effusion (16 patients). Other metastatic sites included the adrenal glands, brain, omentum, and bone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Baseline Characteristics, Diagnostic Markers, and Survival Outcomes of Patients diagnosed with Stage IV Gastric Cancer\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"90%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVariables\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003eTotal population means (N = 134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eMedian (iqr)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e52.4 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e52 (42 \u0026ndash; 63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e93 (69.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e41 (30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eAsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e74 (55.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eMENA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e40 (29.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e20 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e124 (92.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e10 (7.46 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHTN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e95 (70.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e39 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e97 (72.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e37 (27.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA19-9\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1264.4 (2976.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e37.5 (8.85 \u0026ndash; 434.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCEA \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e166.2 (916.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e4.75 (1.9 \u0026ndash; 24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePD-L1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e13.1 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e5 (0 \u0026ndash; 20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMMR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e74 (94.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e4 (5.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifferentiation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e26 (22.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eModerate to poor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e2 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e78 (67.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e10 (8.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignet-ring\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e86 (64.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e48 (35.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHER2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e107 (83.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e21 (16.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall median survival\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003eMonths, (95% UI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e11 (8 \u0026ndash; 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignant lesion site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eBody\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e66 (49.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePylorus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e4 (2.99%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eAntrum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e29 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e35 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePeritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eOmentum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eRPLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eLung/Pleural Effusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eBone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eAdrenal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eOvary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003eBrain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch2\u003eSingle-site metastasis results\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eOnly 40 patients were identified as having a single- site of metastasis distribute as follows; \u0026nbsp;liver (n=16), peritoneum (n=15), and RPLN(n=9) (Figure 1). Table 2 compares the baseline characteristics of these patients. Patients with liver metastasis had a higher median age of 64.0 years (IQR: 54.5\u0026ndash;68.0), while those with peritoneal metastasis were younger, with a median age of 46.0 years (IQR: 40.0\u0026ndash;57.0). The RPLN group had a median age of 57.0 years (IQR: 43.0\u0026ndash;73.0). The liver metastasis group had a higher proportion of males (94%), while the peritoneum and RPLN groups had a lower male prevalence (47% and 78%, respectively).\u003c/p\u003e\n\u003cp\u003eAmong tumor markers, median CA19-9 levels were highest in the peritoneum group at 36.8 U/mL (IQR: 14.8\u0026ndash;94.0), followed by the RPLN group at 32.0 U/mL (IQR: 23.0\u0026ndash;7730.0) (p = 0.32), and liver group at 10.3 U/mL (IQR: 5.0\u0026ndash;7683.0). Median CEA levels differed between the groups, showing statistical divergence (p = 0.043), with the highest levels in the liver metastasis group (13.5 ng/mL, IQR: 2.0\u0026ndash;159.0), compared to the RPLN (2.6 ng/mL, IQR: 1.4\u0026ndash;21.1) and peritoneum groups (1.6 ng/mL, IQR: 1.1\u0026ndash;2.0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTumor differentiation was predominantly poor in all groups, with 64% of patients in the total population exhibiting poor differentiation. The RPLN group had the highest percentage of poor differentiation (71%), followed by the peritoneum group (73%) and liver group (50%) (p = 0.40). Signet-ring cell carcinoma was present in 32% of the total population, with the highest prevalence in the liver group (100%) and lower rates in the peritoneum (47%) and RPLN groups (44%) (p = 0.002). HER2 positivity was similar across groups, with no statistically divergent differences (p = 0.18). PD-L1 positivity varied slightly, with the highest levels in the liver group (median 5%, IQR: 1.1\u0026ndash;10.0) compared to the RPLN group (median 10%, IQR: 5.0\u0026ndash;10.0) and the peritoneum group (median 2%, IQR: 0.0\u0026ndash;3.0) (p = 0.10). MMR deficiency was rare across all groups, indicating non-divergence (p = 0.49). The liver metastasis group had the highest percentage of patients treated for cancer (29%), while the RPLN group had the highest percentage of untreated patients (56%) (p = 0.40). The most common location of primary gastric lesions was the body of the stomach (60%), with statistically non-divergent differences in location distribution across groups (p = 0.71).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Comparison of Characteristics of Patients with Liver-only, Peritoneum-only, and RPLN-only metastasis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003ePeritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003eRPLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eN=40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003eN=16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eN=15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003eN=9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMedian (iqr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e57.0 (43.5-66.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e64.0 (54.5-68.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e46.0 (40.0-57.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e57.0 (43.0-73.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e29 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e15 (94%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e7 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e7 (78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e11 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1 ( 6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e8 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eRegion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e19 (48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e8 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e8 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e3 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eArab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e16 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e8 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e3 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e5 ( 13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e2 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e3 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eCVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e35 (88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e14 (88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e12 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e9 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e5 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e3 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e26 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e11 (69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e10 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e5 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e14 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e5 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e26 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e9 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e11 (73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e6 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e14 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e7 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e4 (27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e3 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eCOPD/asthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e35 (88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e14 (88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e14 (93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e7 (78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e5 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 ( 7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eCA19-9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMedian (iqr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e23.0 (10.3-393.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e10.3 (5.0-7683.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e36.8 (14.8-94.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e32.0 (23.0-7730.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eCEA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMedian (iqr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2.1 (1.4-13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e13.5 (2.0-159.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1.6 (1.1-2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2.6 (1.4-21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eDifferentiation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003emoderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e10 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e6 (43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e2 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003epoor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e23 (64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e7 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e11 (73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e5 (71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e3 ( 8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1 ( 7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e2 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eSignet-ring\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e27 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e16 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e7 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e13 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e8 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e5 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e31 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e11 (69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e11 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e9 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e8 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e5 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e3 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003ePDL1 +ve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMedian (iqr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e4.0 (1.6-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e5.0 (1.1-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e2.0 (0.0-3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e10.0 (5.0-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eMMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e20 (91%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e7 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e9 (90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2 ( 9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0 ( 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e1 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eTreated\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e14 (37%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e4 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e5 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e24 (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e10 (71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e10 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eLocation of primary lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eLower gastric\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e11 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e4 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eMiddle gastric\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e18 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e6 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e9 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e3 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eUpper gastric\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e10 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e5 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch2\u003eSurvival Analysis Results\u003c/h2\u003e\n\u003cp\u003eKaplan\u0026ndash;Meier analysis demonstrated a median overall survival (OS) of 20.7 months in patients with liver-only metastasis, compared to 7.0 months in those with peritoneum-only metastasis and 18.0 months in those with RPLN-only metastasis (Figure 2).\u003c/p\u003e\n\u003cp\u003eIn univariate Cox regression analysis, peritoneum-only metastasis showed statistical divergence compared to liver-only metastasis (HR = 2.87, 95% UI: 1.03\u0026ndash;7.97, \u003cem\u003ep\u003c/em\u003e = 0.04), (Table 3). In contrast, RPLN-only metastasis did not demonstrate statistical divergence (HR = 1.07, 95% UI: 0.32\u0026ndash;3.64, \u003cem\u003ep\u003c/em\u003e = 0.90). After adjusting for age and gender, the association between peritoneum-only metastasis and reduced survival was not statistically divergent (adjusted HR = 2.9, 95% UI: 0.67\u0026ndash;12.69, \u003cem\u003ep\u003c/em\u003e = 0.15), and RPLN-only metastasis remained non-divergent (adjusted HR = 1.22, 95% UI: 0.35\u0026ndash;4.19, \u003cem\u003ep\u003c/em\u003e = 0.75). The wide uncertainty intervals, particularly in the multivariable analysis, reflect a high degree of imprecision, likely due to small subgroup sizes. Intervals that include the null value (HR = 1.0) suggest that the observed effects are also compatible with minimal or no difference in survival (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the Firth-penalized Cox regression model, the site of metastasis was associated with differential overall survival (Table 4). Using liver metastasis as the reference category, patients with peritoneal metastasis demonstrated an increased risk of death (HR = 2.81, 95% UI: 1.05\u0026ndash;7.85, \u003cem\u003ep\u003c/em\u003e = 0.04). In contrast, patients with RPLN metastasis did not exhibit a statistically divergent difference in hazard compared to those with liver metastases (HR = 1.14, 95% UI: 0.32\u0026ndash;3.51, \u003cem\u003ep\u003c/em\u003e = 0.83). These results suggest that peritoneal metastasis may be associated with a worse prognosis relative to liver involvement, while RPLN metastasis appears to confer a similar risk profile.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eUnivariate and Multivariable\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCox-proportional regression analysis comparing single-site metastasis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUnivariate HR (95% UI)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMultivariable HR (95%UI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePeritoneum\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.87 (1.03 \u0026ndash; 7.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.9 (0.67\u0026ndash;12.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRPLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.07 (0.32 \u0026ndash; 3.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.22 (0.35\u0026ndash;4.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003eCompared to liver metastasis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u0026nbsp;\u003c/strong\u003eFirth-penalized Cox-proportional regression analysis comparing single-site metastasis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"71%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHR (95% UI) *\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePeritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.81 (1.05 \u0026ndash; 7.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRPLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.14 (0.32 \u0026ndash; 3.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e*Compared to liver metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first study from the MENA region to examine the clinicopathological characteristics, prognosis, and survival outcomes of advanced-stage gastric cancer with single-site metastasis using real-world data from Qatar. Unlike previous studies, our cohort includes a diverse population comprising individuals from Asian, Middle Eastern Arab, and African backgrounds, offering broader regional insight into metastatic patterns and outcomes. In this study, we analyzed the prognostic outcomes of patients diagnosed with stage IV GC, with a specific focus on those who had single-site of metastasis. Based on our data, liver, peritoneum, and RPLN were the most common sites of metastasis. In the overall sample of patients with GC, the most common site of metastasis was the peritoneum. This is consistent with recent results from a nationwide cancer registry in the Netherlands, which found that 58% of patients with gastric cancer\u0026ndash;related peritoneal metastasis had isolated peritoneal involvement (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In comparison, a 2016 population-based study from Sweden found liver metastasis to be the most common site followed by peritoneum and lung (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The reason for this variation may be due to the difference in patient demographic including race, age distribution, and genetic factors (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe liver-only metastasis group had a higher prevalence of male patients, and older median age compared to those with peritoneum or RPLN metastasis. This is consistent with a previous study suggesting that liver-only metastasis in GC patients tends to occur in older populations (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Additionally, our results show that liver-only metastasis is associated with a favorable prognosis compared to RPLN and peritoneum-only metastasis. Furthermore, studies have shown that GC patients with liver-only metastasis who undergo gastrectomy and/or hepatectomy have further improvement in overall survival (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). However, only two patients in our cohort received surgical intervention, highlighting a potential underutilization of surgery in this subgroup. Future clinical practice should consider selecting appropriate patients with liver-only metastasis for surgical management to potentially enhance survival outcomes.\u003c/p\u003e \u003cp\u003eOur results are consistent with studies utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, which included patients with metastatic GC, found that patients with liver or lung metastasis exhibited better survival(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). However, a more recent study conducted by Wang et al. using the SEER database found that liver metastasis was an adverse prognostic factor for OS. Additionally, their multivariable Cox proportional hazard ration revealed that patients with liver metastasis had a much worse survival compared to lung-only(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Although we did not compare liver-only metastasis to other sites such as lung, we found that liver-only metastasis had better OS in the overall population. A more recent 2024 retrospective study based on SEER database found liver metastasis to be the most common single organ metastasis, and bone metastasis leading to the worst OS (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Within our sample, we found that peritonea-only metastasis had the worst OS compared to both liver-only and RPLN-only metastasis. In a Dutch registry (2015\u0026ndash;2020), patients with isolated peritoneal metastases had a median OS of only 4.4 months, nearly identical to those with isolated non-peritoneal metastases (4.6 months), with an adjusted HR\u0026thinsp;\u0026asymp;\u0026thinsp;0.94 (p\u0026thinsp;=\u0026thinsp;0.185) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A systematic review found that the median OS for gastric peritoneal metastases ranged from 2\u0026ndash;9 months(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Furthermore, our study shows that patients with signet-ring cell positive are at a higher risk of peritoneal metastasis which is consistent with previous studies (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdditionally, our results suggest that tumor markers such as CA19-9, CEA, and PD-L1 expression vary depending on the site of metastasis. Specifically, CA19-9 levels were higher in patients with RPLN-only and peritoneum-only metastasis compared to liver-only metastasis (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Previous studies have shown it to be strongly associated with lymph-node, peritoneal ,and serosal involvement (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Elevated tumor markers predict peritoneal disease. In a series of advanced GC patients, 80.6% of those with CA125\u0026thinsp;\u0026ge;\u0026thinsp;35 U/mL had peritoneal metastasis, and high CA125 was associated with shorter survival (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Recent studies have shown that combining CEA, CA19-9, and CA72-4 may help in improving the prognostic value compared with using a single tumor marker (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Notably, a recent study found that nearly one-third of HER2-negative primary tumors converted to HER2-low in metastatic lesions, particularly in metachronous liver and lung metastases (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). This evolution has important clinical implications, as it could expand eligibility for HER2-targeted antibody-drug conjugate (ADC) therapies, such as trastuzumab deruxtecan, which have shown efficacy in HER2-low expressing tumors. Therefore, re-evaluating HER2 status in metastatic lesions, especially in non-peritoneal sites like the liver, is crucial when considering systemic treatment strategies.\u003c/p\u003e \u003cp\u003eOur study has several limitations, including the retrospective nature of the data and the small sample size, particularly in subgroup analyses. These factors may introduce bias and limit the generalizability of our findings. Nevertheless, the study offers several notable strengths. Importantly, despite the limited sample size (N\u0026thinsp;=\u0026thinsp;40), we observed a statistically divergent association between peritoneum-only metastasis and worse overall survival compared to liver-only metastasis in both Kaplan-Meier and univariate Cox regression analyses. However, multivariable models had wider uncertainty intervals, reflecting reduced statistical power and the need for cautious interpretation. Further large cohort studies are needed to examine how combined molecular markers, and metastatic patterns influence prognosis in advanced-stage gastric cancer. In addition, future research should explore how metastatic patterns can inform a more individualized, patient-centered approach to treatment selection.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGC: Gastric cancer\u003c/p\u003e\n\u003cp\u003eOS: Overall survival\u003c/p\u003e\n\u003cp\u003emOS: Median overall survival\u003c/p\u003e\n\u003cp\u003eRPLN: Retroperitoneal lymph nodes\u003c/p\u003e\n\u003cp\u003eIRB: Institutional Review Board\u003c/p\u003e\n\u003cp\u003eNCCCR: National Center for Cancer Care and Research\u003c/p\u003e\n\u003cp\u003eHMC: Hamad Medical Corporation\u003c/p\u003e\n\u003cp\u003eCT: Computed tomography\u003c/p\u003e\n\u003cp\u003ePET: Positron emission tomography\u003c/p\u003e\n\u003cp\u003eMMR: Mismatch repair\u003c/p\u003e\n\u003cp\u003ePD-L1: Programmed death-ligand 1\u003c/p\u003e\n\u003cp\u003eHER2: Human epidermal growth factor receptor 2\u003c/p\u003e\n\u003cp\u003eCEA: Carcinoembryonic antigen\u003c/p\u003e\n\u003cp\u003eCA19-9: Carbohydrate antigen 19-9\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eData Availability statement\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to ethical and institutional restrictions related to patient confidentiality but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eConflict of interest statement\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003ch2\u003eFunding Statement\u003c/h2\u003e\n\u003cp\u003eThe authors declare that this study received no external funding.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution Statement (CRediT)\u003c/h2\u003e\n\u003cp\u003eConceptualization was carried out by A.S., A.A., K.R., and S.B. Methodology development and formal analysis were performed by L.A.Z., A.S., and N.E.O. Data curation and investigation were handled by M.S.E., S.A.A., M.M., E.T., A.A., A.S., and K.R. Visualization was prepared by L.A.Z., A.S., and N.E.O. Resources and project administration were provided by A.S., K.R., S.B., W.A., R.A., A.J., and M.M. Supervision of the study was conducted by S.A., M.S.E., S.A.A., A.J., R.A., W.A., A.A., and M.M. The original draft of the manuscript was written by L.A.Z., A.A., A.S., and N.E.O., and all authors contributed to the review and editing of the final manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003ch2\u003eEthics and Informed Consent Statement\u003c/h2\u003e\n\u003cp\u003eThe study protocol was approved by the Institutional Review Board (IRB) of Hamad Medical Corporation (MRC-01-24-522). The study was conducted in accordance with the principles of the Declaration of Helsinki. In accordance with IRB guidelines, informed consent was waived due to the retrospective design of the study.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eThe authors would like to thank the National Center for Cancer Care and Research at Hamad Medical Corporation for providing access to clinical data and institutional support. We also acknowledge the multidisciplinary oncology teams involved in the care of the patients included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eAoude M, Mousallem M, Abdo M, Youssef B, Kourie HR, Al-Shamsi HO. Gastric cancer in the Arab World: a systematic review. East Mediterr Health J. 2022 Jul 30;28(7):521\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eSmyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet Lond Engl. 2020 Aug 29;396(10251):635\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eAlorabi MO, El-Bassiouny M, Khodary DAEGE, Din MMAEE, Elsayed AMMA, Reda C. Clinical presentation and treatment outcomes of gastric adenocarcinoma patients: a retrospective study from Ain Shams Clinical Oncology Department [Internet]. 2025 [cited 2025 May 30]. Available from: http://ecancer.org/en/journal/article/1861-clinical-presentation-and-treatment-outcomes-of-gastric-adenocarcinoma-patients-a-retrospective-study-from-ain-shams-clinical-oncology-department\u003c/li\u003e\n\u003cli\u003eBaba H, Kuwabara K, Ishiguro T, Kumamoto K, Kumagai Y, Ishibashi K, et al. Prognostic Factors for Stage IV Gastric Cancer. Int Surg. 2013;98(2):181\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSalati M, Valeri N, Spallanzani A, Braconi C, Cascinu S. Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications. Eur J Surg Oncol. 2019 Aug 1;45(8):1479\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eAl-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, et al. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eZhan PL, Canavan ME, Ermer T, Pichert MD, Li AX, Maduka RC, et al. Association Between Metastatic Pattern and Prognosis in Stage IV Gastric Cancer: Potential for Stage Classification Reform. Ann Surg Oncol. 2023 Jul 1;30(7):4180\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eRiihim\u0026auml;ki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K. Metastatic spread in patients with gastric cancer. Oncotarget. 2016 Jul 20;7(32):52307\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eStataCorp. College Station, TX; 2023. (Stata Statistical Software). \u003c/li\u003e\n\u003cli\u003eZar LA, Abdulmajeed J, Elshoeibi AM, Syed A, Awaisu A, Glasziou P, et al. From significance to divergence: guiding statistical interpretation through language. Curr Opin Epidemiol Public Health. :10.1097/PXH.0000000000000050. \u003c/li\u003e\n\u003cli\u003eGelman A, Greenland S. Are confidence intervals better termed \u0026ldquo;uncertainty intervals\u0026rdquo;? 2019 Sep 10 [cited 2025 Jun 8]; Available from: https://www.bmj.com/content/366/bmj.l5381\u003c/li\u003e\n\u003cli\u003eGuchelaar NAD, de Neijs MJ, Noordman BJ, Graaf HEC, van Hellemond IEG, van der Sluis PC, et al. The prognostic value of peritoneal metastases in patients with gastric cancer: a nationwide population-based study. EClinicalMedicine. 2025 Mar;81:103109. \u003c/li\u003e\n\u003cli\u003eTseng JF, Mansfield PF, Feig BW, Pisters PW, Ajani JA, Yao JC. The effect of ethnicity on presentation, pattern of metastasis, and survival in gastric adenocarcinoma at a single center. J Clin Oncol. 2004 Jul 15;22(14_suppl):4016\u0026ndash;4016. \u003c/li\u003e\n\u003cli\u003eKlapheke AK, Carvajal-Carmona LG, Cress RD. Racial/Ethnic Differences in Survival among Gastric Cancer Patients in California: Gastric Cancer Survival by Race. Cancer Causes Control CCC. 2019 Jul;30(7):687\u0026ndash;96. \u003c/li\u003e\n\u003cli\u003eGonzalez‐Pons M, Torres‐Cintr\u0026oacute;n CR, Soto‐Salgado M, Vargas‐Ramos Y, Perez‐Portocarrero L, Morgan DR, et al. Racial/ethnic disparities in gastric cancer: A 15‐year population‐based analysis. Cancer Med. 2022 Jul 3;12(2):1860\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eEl Halabi M, Horanieh R, Tamim H, Mukherji D, Jdiaa S, Temraz S, et al. The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre. J Gastrointest Oncol. 2020 Dec;11(6):1233\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eZhang H, Cheng X, Guo W, Zheng C, Zhang Y, Jing X, et al. Metastasis patterns and prognosis in young gastric cancer patients: A propensity score‑matched SEER database analysis. PLOS ONE. 2024 Apr 9;19(4):e0301834. \u003c/li\u003e\n\u003cli\u003eSun W, Li X. Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population‐Based, Case‐Control Study. Health Sci Rep. 2024 Dec 12;7(12):e70220. \u003c/li\u003e\n\u003cli\u003eTakahashi K, Terashima M, Notsu A, Koseki Y, Furukawa K, Fujiya K, et al. Surgical treatment for liver metastasis from gastric cancer: A systematic review and meta-analysis of long-term outcomes and prognostic factors. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2024 Oct;50(10):108582. \u003c/li\u003e\n\u003cli\u003eLi Y, Xie D, Chen X, Hu T, Lu S, Han Y. Prognostic Value of the Site of Distant Metastasis and Surgical Interventions in Metastatic Gastric Cancer: A Population-Based Study. Technol Cancer Res Treat. 2020;19:1533033820964131. \u003c/li\u003e\n\u003cli\u003eWang J, Li S, Liu Y, Zhang C, Li H, Lai B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population‐based analysis. Cancer Med. 2019 Nov 6;9(1):361\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eZhao QW, Quan Z, Liu SS, Wang YD, Guo HN. Heterogeneity and prognosis of single organ metastases in gastric cancer. Transl Gastroenterol Hepatol. 2024 Sep 25;9:61. \u003c/li\u003e\n\u003cli\u003eRijken A, Lurvink RJ, Luyer MDP, Nieuwenhuijzen GAP, van Erning FN, van Sandick JW, et al. The Burden of Peritoneal Metastases from Gastric Cancer: A Systematic Review on the Incidence, Risk Factors and Survival. J Clin Med. 2021 Oct 23;10(21):4882. \u003c/li\u003e\n\u003cli\u003eThomassen I, van Gestel YR, van Ramshorst B, Luyer MD, Bosscha K, Nienhuijs SW, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014 Feb 1;134(3):622\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eHasbahceci M, Malya F, Kunduz E, Guler M, Unver N, Akcakaya A. Use of serum and peritoneal CEA and CA19-9 in prediction of peritoneal dissemination and survival of gastric adenocarcinoma patients: are they prognostic factors? Ann R Coll Surg Engl. 2018 Apr;100(4):257\u0026ndash;66. \u003c/li\u003e\n\u003cli\u003eUcar E, Semerci E, Ustun H, Yetim T, Huzmeli C, Gullu M. Prognostic value of preoperative CEA, CA 19-9, CA 72-4, and AFP levels in gastric cancer. Adv Ther. 2008 Oct;25(10):1075\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eYamamoto M, Baba H, Toh Y, Okamura T, Maehara Y. Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients. J Cancer Res Clin Oncol. 2007 Jul;133(7):471\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eUeda A, Yuki S, Ando T, Hosokawa A, Nakada N, Kito Y, et al. CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer. Cancers. 2024 Jan;16(5):871. \u003c/li\u003e\n\u003cli\u003eZhang R, Chen X, Chen G, Zhao Z, Wei Y, Zhang F, et al. Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality. Ann Surg Oncol. 2023 Dec;30(13):8561\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003eHe WZ, Yang YZ, Yin CX, Xian XY, Gu JM, Yi JH, et al. Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions. Npj Precis Oncol. 2025 Apr 15;9(1):1\u0026ndash;8. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8696557/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8696557/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eAlthough recent studies have shown a steady decline in mortality over the past several decades, Gastric cancer (GC) remains the fifth major cause of cancer-related mortality. Several prognostic factors, both patient- and tumor-related have been investigated as predictors for survival in patients with stage 4 GC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim\u003c/strong\u003e: In this study, we aim to investigate whether the site of metastasis in patients newly diagnosed with stage 4 GC is a predictor for length of survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This is a retrospective cohort study of patients treated at the National Center for Cancer Care and Research, Doha, Qatar. The data was collected between January 2015 and December 2020. We generated three groups, each including patients with metastasis to a single site: liver, peritoneum, or retroperitoneal lymph nodes (RPLN). A Kaplan-Meier survival graph was used to illustrate the overall survival of patients in the three groups. Cox proportional-hazard model was used to investigate whether site of metastasis is a predictor for overall survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 134 patients with a median age of 52 (42 – 63) were diagnosed with stage IV GC. As for differentiation, around 67% had poorly differentiated GC. Of the 134 patients with Stage IV GC, 40 patients had single-site metastasis to either the liver, peritoneum, or RPLN. The Kaplan-Meier curve showed a statistically divergent increase in median overall survival (mOS) in patients with metastasis to the liver compared to peritoneum (20 vs 7, p = 0.03). Furthermore, patients with peritoneum-only metastasis had a 2.87-fold (95% UI 1.03 – 7.97, p = 0.043) increased mortality compared to liver-only metastasis. Patients with RPLN-only had similar survival compared to liver-only metastasis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This study shows that patients with liver-only or RPLN-only metastasis have a better mOS compared to peritoneal. As our data is from a single center, further analysis of large cohorts is needed to validate the findings.\u003c/p\u003e","manuscriptTitle":"Clinicopathological Characteristics, Prognosis, and Survival Outcomes of Advanced Stage Gastric Cancer with Single- Site Metastasis: Nationwide Real-World Data from Qatar","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-12 07:22:30","doi":"10.21203/rs.3.rs-8696557/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-09T08:54:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24618648447432561305676290800973556343","date":"2026-03-08T06:39:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-07T03:12:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311798553811590970458071052204986955955","date":"2026-03-07T02:12:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-05T16:44:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-05T06:09:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-06T21:40:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-06T11:55:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-02-06T11:08:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e77c29bd-37fd-44d9-a769-ccc1552d6cc7","owner":[],"postedDate":"March 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-12T07:22:31+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-12 07:22:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8696557","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8696557","identity":"rs-8696557","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}