{"paper_id":"0d680ce2-04d2-46fc-a58e-8e8b49dd91a5","body_text":"Association Between Radiotherapy and Non-Gastric Second Primary Malignancies in Patients with Resectable Gastric Cancer : A propensity-adjusted, population-based SEER analysis | 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 Association Between Radiotherapy and Non-Gastric Second Primary Malignancies in Patients with Resectable Gastric Cancer : A propensity-adjusted, population-based SEER analysis Li Li, Yunhe Gao, Hua Li, Benlong Zhang, Zijian Wang, ErPeng Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4747305/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background The study aims to investigate the relationship between radiotherapy (RT) and the risk of second primary malignancies (SPMs) in GC patients, and assess the prognostic impact of RT. Patients and methods: We retrieved data on patients with primary GC from the SEER database. The study focused on the association between RT and the occurrence of hematologic malignancies at least 2 years post-diagnosis, as well as the emergence of solid cancers at least 5 years post-diagnosis. For the analysis, we employed competing risk regression analysis and Poisson regression following propensity score matching, along with implemented stratified analysis. Furthermore, we evaluated the impact of RT on the prognosis of GC patients using Kaplan-Meier and Cox regression analysis. Results A total of 24,390 surgically treated patients with pathologically confirmed GC were enrolled in the study. The median OS was 37.0 months (95%CI 16.0-100.0) in the RT group and 24.0 months (IQR, 8.0–24.0) in the NRT group (HR = 0.77, 95%CI 0.74–0.80, P < 0.001). Among the survivors who lived beyond 2 years, 56 (0.70%) were diagnosed with second hematologic malignancies. Additionally, both competing risks and Poisson regressions indicate that RT is not linked to second hematologic malignancies (HR = 0.96, 95%CI: 0.57–1.62, P = 0.87; RR = 0.99, 95%CI: 0.59–1.69, P = 0.97). In 5-year survivors, 362 (7.10%) were diagnosed with second primary solid malignancies, and RT was also not associated with overall second solid malignancies (HR = 1.05, 95%CI, 0.86–1.32, P = 0.61; RR = 1.10, 95%CI, 0.89–1.35, P = 0.39). In subgroup analyses, no association was found between RT and SPM occurrence at any site, and no specific population was identified regarding the effect of RT on the development of SPMs. Conclusion RT improves the prognosis for patients with resectable GC, with no evidence of increasing the risk of developing second primary hematologic or solid malignancies. Stomach neoplasms Second primary malignancies Radiotherapy Surveillance Epidemiology and End Results (SEER) Figures Figure 1 Figure 2 Figure 3 Background Gastric cancer (GC) is one of the most prevalent malignancies and stands as one of the top four contributors to tumor-related fatalities worldwide [ 1 ] . While curative gastrectomy and regional lymph node dissection (LND) are recognized as crucial for the standardized management of resectable GC, a significant proportion of patients still experience recurrence, resulting in unfavorable prognoses [ 2 , 3 ] . Therefore, in effort to improve the limited survival rates among patients afflicted with this condition, multimodal adjuvant therapeutic strategies have undergone thorough examination and received widespread approval [ 4 – 6 ] . More precisely, the incorporation of perioperative chemotherapy or radiotherapy has been found to significantly optimize surgical outcomes [ 7 – 9 ] . However, the role of radiotherapy (RT) alone in the improvement of the prognosis of GC has recently been questioned [ 10 – 12 ] . Given this backdrop, the potential side effects of RT become paramount in decision-making, necessitating a careful assessment of the advantages and disadvantages of RT. The occurrence of second primary malignancies (SPMs), which are tumors that develop independently after an initial malignancy and are not the result of metastasis or recurrence, can have a significant impact on the quality of life and long-term survival prospects of patients with GC. Recent studies have demonstrated that RT notably increases the likelihood of developing SPMs across various cancer types, including rectal [ 13 – 15 ] , breast [ 16 – 19 ] , and lung cancer [ 20 , 21 ] . The occurrence of SPMs associated with RT, though infrequent, is a late-emerging complication that warrants attention. However, there have been limited studies concerning whether RT for GC poses an elevated risk for the development of SPMs. This study employed various methods to evaluate the risk of radiotherapy-associated SPMs and analyze its impact on the prognosis of resectable GC, using the Surveillance, Epidemiology, and End Results (SEER) database. This aspect, infrequently addressed in prior studies, holds significance for guiding the selection of RT for GC. Methods Participant cohorts and cohort definition The SEER database comprises publicly accessible and anonymized data, thereby eliminating the necessity for patient consent or institutional review board approval(Human Ethics and Consent to Participate declarations: not applicable). Throughout its entirety, the study adhered strictly to the Strengthening Reporting Guidelines for Observational Studies in Epidemiology(STROBE) [ 22 ] . This study utilized data from 17 registries in the SEER database, covering patients diagnosed with GC as the first primary cancer between January 2000, and December 2020. Patient diagnoses were pathologically confirmed and coded according to the ICD-O-3 site codes (C16.9). The tumor staging for the included individuals was confined to localized and regional stages, and all of them were undergoing surgical treatment. Exclusion criteria included age less than 20 years or more than 85 years, patients with distant metastases, other types of gastric tumors (gastric mesenchymal tumors, gastric neuroendocrine tumors), other RT regimens, significant missing information, e.g. clinical characteristics, treatment strategies or survival information, mainly including age at gastric cancer diagnosis, race, tumor stage, radiation therapy, year of diagnosis, chemotherapy, survival time, and survival status, etc. Following the prescribed treatment protocol, patients were categorized into two groups: the radiotherapy (RT) group, including GC patients who underwent surgery and perioperative external beam radiotherapy, and a non-radiotherapy (NRT) group, comprising GC patients who underwent surgery only. Outcome and Follow-up The primary outcome of this study was defined as the occurrence of second primary malignancies (SPMs), including either second hematologic malignancies or second solid malignancies, at two or five years post-diagnosis of the initial malignancy, respectively. The determination of the cutoff for survival time was based on the minimum latency period observed for radiation-induced tumorigenesis [ 23 ] . To comprehensively evaluate the risk of SPMs development, we initially examined the risk of all second hematological or solid malignancies. Subsequently, we classified specific tumors based on their site and organ system to estimate the risk of distinct types of SPMs. Apart from the primary endpoint of SPMs, overall survival (OS) and disease-specific survival (DSS) were designated as secondary outcomes. OS refers to the duration commencing from the GC diagnosis until demise due to any cause, whereas DSS denotes the elapsed time from GC diagnosis until death solely attributed to the primary malignancy. Statistical analysis Continuous variables were represented as medians along with interquartile ranges (IQR), and analyzed using the Mann-Whitney U test. Categorical variables were described in frequencies and percentages, and their analysis employed either the χ 2 or Fisher’s exact test. Propensity score matching(PSM) with a caliper width of 0.01 was employed to achieve a 1:1 ratio matching of the two groups, with the objective of minimizing potential bias in the comparison of second primary tumor incidence and prognosis. To assess the prognosis of RT in GC patients, we utilized the Kaplan-Meier method for survival curve generation and conducted a log-rank test to derive the corresponding P-values. Furthermore, a comprehensive evaluation of RT's influence on prognosis was carried out through variable screening and confounder control, employing both univariate and multivariate survival analyses. Fine-Gray competing risk regression analysis was employed to assess the cumulative incidence of SPMs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of SPMs were calculated, considering all-cause death as competing events. Through subgroup analysis of competing risks, we attempted to identify the population potentially affected by radiation therapy, and the results are presented in a forest plot. Additionally, we conducted Poisson regression analyses to assess the relative risks (RRs) and 95% CIs of SPMs in GC patients who underwent RT, in comparison to those who did not. To further assess the dynamic risk of SPMs associated with RT, we estimated the risk based on latency since diagnosis, age at diagnosis, and year of diagnosis, stratifying the RRs. Statistical analysis was conducted using R software (version 4.2.2). A two-tailed p-value of < 0.05 was considered as indicative of statistical significance. Results Patient Characteristics Initially, a total of 37,487 GC patients were identified. Following stringent inclusion and exclusion criteria, the final cohort included 24,390 patients in the study (eFigure 1), in which the median age was 67 years (IQR, 57–75 years). Among them, 15,619 patients (64.0%) were male. Additionally, 15,878 patients (65.1%) were in the NRT group, while 8,512 patients (34.9%) were in the RT group. The baseline characteristics of the treatment modalities of GC patients are detailed in eTable 1. Following the 1:1 PSM, a total of 7113 patients were included in both the RT and NRT groups. These patients exhibited balanced and comparable baseline characteristics, as detailed in eTable 2. Survival Outcome The findings revealed that patients receiving RT had a median OS of 38 months and a DSS of 47 months. The 3-year OS and DSS rates were 51.4% and 55.6%, respectively, while the 5-year rates were 40.4% and 46.3%. In contrast, patients in the NRT group had a median OS of 25 months and a DSS of 32 months. The 3-year OS and DSS rates were 41.6% and 47.4%, while five-year rates were 32.8% and 39.9%. The difference in OS and DSS between the two groups was statistically significant (P < 0.001), as shown in Fig. 1. Furthermore, survival analysis indicated that RT played an active role in the treatment of GC and significantly improved OS and DSS of patients, as shown in eTable 3 and eTable 4. Cumulative Incidences of SPMs Following a 2-year latency, second hematologic malignancies manifested in 31 (0.70%) patients in the RT group and 25 (0.70%) patients in the NRT group, as detailed in Table 1 and eTable 5. After a latency period of 5 years, second solid malignancies occurred in 209 (7.40%) patients in the RT group and 134 (6.80%) patients in the NRT group. The baseline characteristics of patients developing second solid malignancies are displayed in Table 2 and eTable 6. Table 1 Comparisons of characteristics of different treatment modalities in patients with gastric cancer after PSM and surviving more than 2 years. Characteristic NRT, no. (%) RT, no. (%) P value (N = 3577) (N = 4483) Sex 0.279 a Female 1152 (32.2%) 1496 (33.4%) Male 2425 (67.8%) 2987 (66.6%) Age at GC diagnosis, yrs 0.025 a 20–49 617 (17.2%) 673 (15.0%) 50–69 2001 (55.9%) 2571 (57.4%) 70–84 959 (26.8%) 1239 (27.6%) Race 0.363 a White 2404 (67.2%) 2950 (65.8%) Black 411 (11.5%) 552 (12.3%) Other 762 (21.3%) 981 (21.9%) Calendar year of GC diagnosis 0.118 a 2000–2004 1114 (31.1%) 1426 (31.8%) 2005–2009 1062 (29.7%) 1399 (31.2%) 2010–2015 1401 (39.2%) 1658 (37.0%) Tumor location 0.014 a Esophagogastric junction 1182 (33.0%) 1366 (30.5%) Stomach 2395 (67.0%) 3117 (69.5%) Tumor stage < 0.001 a Localized 1011 (28.3%) 950 (21.2%) Regional 2566 (71.7%) 3533 (78.8%) Tumor grade < 0.001 a Grade I/II 1231 (34.4%) 1322 (29.5%) Grade III/IV 2109 (59.0%) 2962 (66.1%) Unknown 237 (6.6%) 199 (4.4%) Tumor size, cm < 0.001 a < 2.0 559 (15.6%) 341 (7.6%) 2.0-4.9 1332 (37.2%) 1816 (40.5%) > 5.0 1201 (33.6%) 1751 (39.1%) Unknown 485 (13.6%) 575 (12.8%) Tumor histology < 0.001 a Adenocarcinoma 2678 (74.9%) 3308 (73.8%) Mucous tumor 772 (21.6%) 1087 (24.2%) Others 127 (3.6%) 88 (2.0%) Chemotherapy < 0.001 a No 2176 (60.8%) 268 (6.0%) Yes 1401 (39.2%) 4215 (94.0%) Second hematologic malignancies 25 (0.7%) 31 (0.7%) 1.000 a Latency, mo, median (IQR) 72.0 (48.0-116.0) 73.0 (52.0-136.5) 0.680 b Survival.monthsr, mo, median (IQR) 77 (42–130) 80 (42–135) 0.053 b NOTE: P values were calculated using χ2 test (a) for categorical variables and the Mann-Whitney U test (b) for continuous variables of skewed distributions. Abbreviations: PSM, propensity score matching; RT, radiation therapy; NRT, no radiation therapy; GC, gastric cancer; yrs, years old; IQR, interquartile range. Table 2 Comparisons of characteristics of different treatment modalities in patients with gastric cancer after PSM surviving more than 5 years. Characteristic NRT, no. (%) RT, no. (%) P value (N = 2259) (N = 2814) Sex 0.159 a Female 714 (31.6%) 943 (33.5%) Male 1545 (68.4%) 1871 (66.5%) Age at GC diagnosis, yrs 0.032 a 20–49 414 (18.3%) 438 (15.6%) 50–69 1288 (57.0%) 1652 (58.7%) 70–84 557 (24.7%) 724 (25.7%) Race 0.097 a White 1503 (66.5%) 1791 (63.6%) Black 264 (11.7%) 351 (12.5%) Other 492 (21.8%) 672 (23.9%) Calendar year of GC diagnosis 0.011 a 2000–2004 698 (30.9%) 899 (31.9%) 2005–2009 659 (29.2%) 902 (32.1%) 2010–2015 902 (39.9%) 1013 (36.0%) Tumor location < 0.001 a Esophagogastric junction 753 (33.3%) 794 (28.2%) Stomach 1506 (66.7%) 2020 (71.8%) Tumor stage < 0.001 a Localized 816 (36.1%) 688 (24.4%) Regional 1443 (63.9%) 2126 (75.6%) Tumor grade < 0.001 a Grade I/II 845 (37.4%) 864 (30.7%) Grade III/IV 1246 (55.2%) 1820 (64.7%) Unknown 168 (7.4%) 130 (4.6%) Tumor size, cm < 0.001 a < 2.0 452 (20.0%) 242 (8.6%) 2.0-4.9 850 (37.6%) 1177 (41.8%) > 5.0 660 (29.2%) 1058 (37.6%) Unknown 297 (13.1%) 337 (12.0%) Tumor histology < 0.001 a Adenocarcinoma 1729 (76.5%) 2107 (74.9%) Mucous tumor 436 (19.3%) 650 (23.1%) Others 94 (4.2%) 57 (2.0%) Chemotherapy < 0.001 a No 1452 (64.3%) 176 (6.3%) Yes 807 (35.7%) 2638 (93.7%) Second solid malignancies 153 (6.8%) 209 (7.4%) 0.398 a Latency, mo, median (IQR) 98.0 (72.0-131.0) 102.0 (78.0-138.0) 0.210 b Survival.monthsr, mo, median (IQR) 114 (81–162) 119 (86–165) 0.005 b NOTE: P values were calculated using χ2 test (a) for categorical variables and the Mann-Whitney U test (b) for continuous variables of skewed distributions. Abbreviations: PSM, propensity score matching; RT, radiation therapy; NRT, no radiation therapy; GC, gastric cancer; yrs, years old; IQR, interquartile range. Two years after a GC diagnosis, the cumulative incidence of hematologic malignancies was 0.70%. Notably, hematologic malignancies showed a cumulative incidence of 0.70% among RT-receiving patients, contrasting with 0.70% among those without RT (P = 0.868, refer to Fig. 2). The cumulative incidence of malignancies for solid tumors was 7.14%. In the RT group, this value was 7.43%, while patients without RT exhibited a cumulative incidence of 6.77% for second solid malignancies (P = 0.618, see Figure. 2). In location-specific analysis, no statistically significant difference was observed in the cumulative incidence rate of major solid tumors between the RT and NRT groups (P > 0.05, eFigure 2). Correlation of Radiotherapy with SPMs Univariate competing risks regression analysis was conducted, encompassing all variables listed in eTable 7 and eTable 8. Inclusion of statistically significant variables in univariate analysis, as well as the RT in the multivariate analysis. The results indicated that the incidence of second primary hematological or solid malignancies was not linked to RT (HR = 0.96, 95% CI, 0.57–1.62, P = 0.87; HR = 1.05, 95% CI, 0.86–1.30, P = 0.61). In the subgroup stratified by clinicopathological features, RT was not associated with the development of SPMs, as shown in Fig. 3 and eFigure 3 (eTable 9 and eTable 10). In Poisson regression analysis, the adjusted RR was computed to verify the association between the risk of SPMs and RT, taking into account the modifying effects of patient age, sex, and the calendar year at the time of GC diagnosis. The adjusted RR for the additional risk of combined second primary hematological malignancies was found to be 1.04 (95% CI, 0.61–1.78, P = 0.89), with the adjusted RR of second primary solid malignancies ( RR = 1.09, 95% CI, 0.88–1.34, P = 0.44) (Table 3 ). Table 3 Statistical analysis of the risk of development of SPMs in patients with gastric cancer Variables Multivariable Competing Risk Regression (RT vs NRT) Poisson regression (RT vs NRT) Poisson regression (RT vs NRT) HR (95% CI) P value RR (95% CI) P value Adjusted RR (95% CI) P value Secondary hematologic malignancies 0.96(0.57–1.62) 0.87 0.99(0.59–1.69) 0.97 1.04(0.61–1.78) 0.89 Secondary solid malignancies 1.05(0.86–1.30) 0.61 1.10(0.89–1.35) 0.39 1.09(0.88–1.34) 0.44 NOTE: Fine-Gray competing risk regression analyses were conducted to ascertain the HR and 95% CI for SPMs in GC patients undergoing RT, in contrast to those who did not. The variable pertaining to RT, along with statistically significant covariates identified via univariate competing risks regression analyses (P < 0.05), were subsequently incorporated into the multivariate analysis. Poisson regression analysis was used to assess the RR and 95%CI of SPMs in patients who underwent RT vs. those who did not. Similarly, in the calculation of RRs as well as 95% CIs for patients with RT and NRT from Poisson regression analyses, we have adjusted for age, sex, and the calendar year at the time of GC diagnosis. Abbreviations: SPMs, second primary malignancies; GC, gastric cancer; RT, radiation therapy; NRT, no radiation therapy; HR, hazard ratio; RR, radiotherapy-associated risk. Dynamic Risk Evaluation for SPMs After in-depth analysis of three dynamic RR plots for age at GC diagnosis, year of diagnosis, and latency, we observed that RT did not significantly increase the risk of SPMs at any stage. However, the trends for second primary haematological and second primary solid malignancies showed some variability. In the dynamic age-adjusted RR plot, the risk of developing a second primary solid malignancies in GC patients receiving RT, as depicted in Fig. 5 (20–49 year-old: adjusted RR = 1.13, 95% CI 0.59–2.16, P = 0.717; 50–69 year-old: adjusted RR = 1.01, 95% CI 0.78–1.32, P = 0.917; 70–84 year-old: adjusted RR = 1.17, 95% CI 0.76–1.85, P = 0.483). However, the risk of haematological malignancies in the 20–49 age group could not be accurately assessed due to sample size limitations. RR plot for second primary haematological malignancies in other age groups is in Fig. 5 (50–69 year-old: adjusted RR = 1.86, 95% CI 0.47–1.86, P = 0.838; 70–84 year-old: adjusted RR = 1.24, 95% CI 0.52–3.17, P = 0.631). Analysis of dynamic year of diagnosis-adjusted RR plot shows that second primary haematological malignancies differ from solid malignancies in their trends. The risk of haematological malignancies appears to decrease gradually over years. However, the risk of developing a second primary malignancy in patients treated with RT varies with the calendar years since diagnosis (2000–2004: adjusted RR = 1.63, 95% CI 0.68–4.32, P = 0.290; 2005–2009: adjusted RR = 1.18, 95% CI 0.51–2.85, P = 0.711; 2010–2015: adjusted RR = 0.40, 95% CI 0.12–1.32, P = 0.134). In the dynamic latency-RR plot, no significant changes were observed for haematological and solid malignancies with latency. In addition, the RR results of the SPMs in patients treated with RT was similar to the adjusted RR plots (eFigures 4, eTable 11 and eTable 12 in the Supplementary Appendix). Discussion Radiotherapy is a crucial component of the comprehensive treatment for GC, contributing significantly to overall treatment outcomes [ 6 , 24 ] . However, the potential toxic effects of RT on patients should not be ignored, especially the radiation exposure associated with RT may lead to the development of SPMs, an easily overlooked complication. Despite advancements in RT techniques mitigating inadvertent irradiation of adjacent normal tissues, some studies [ 15 , 25 , 26 ] indicate an increased risk of SPMs after RT for specific cancers. In this study, leveraging data from a substantial population-based cohort, we employed various methods to unravel the intricate relationship between RT and individual SPMs risk in resectable GC patients, simultaneously evaluating the prognostic impact of RT on primary GC patients. Our findings indicate that RT not only does not increase the risk of developing second primary hematologic or solid malignancies in GC patients but also improves OS and DSS in these individuals. RT is widely acknowledged as a significant risk factor for specific SPMs across various primary cancer types. For instance, in a study by Guan et al [ 13 ] , involving 20,142 female patients with rectal cancer as the first primary cancer who survived for at least 5 years, various ways of statistical analysis revealed a significant increase in the risk of uterine corpus and ovarian cancer following RT. On a different note, Zhou et al [ 20 ] . analyzed 62,435 patients with nonmetastatic lung cancer who underwent surgery, demonstrating a significant association between RT and an increased risk of major second primary malignant tumors (RR = 1.21; 95% CI, 1.08–1.35), particularly in the development of second primary gastrointestinal malignancies (RR = 1,77, 95%CI: 1.44–2.15). Conversely, there was no association with the development of second hematologic malignancies (RR = 1.08, 95% CI: 0.84–1.37). In the context of the SPMs in GC, Chen et al [ 27 ] . identified RT as an independent risk factor for SPMs in a study involving 137,798 participants from the Taiwan National Health Insurance database. Binay et al [ 28 ] . conducted an evaluation of 33,720 patients drawn from the SEER 13 database, employing standardized incidence rate ratios (SIRs). Their research has demonstrated a significantly elevated risk of developing SPMs among GC patients in the United States, when compared to the general population. Additionally, the research highlighted a noteworthy increase in SPMs risk during RT for GC. Similarly, Jin et al [ 29 ] . analyzed data on patients diagnosed with gastric adenocarcinoma (GAC) in the SEER database from 2000 to 2020. The results showed that patients with GAC had a significantly increased risk of developing SPMs, with a SIRs of 1.36, 95% CI of 1.32–1.40 and an excess incidence risk (EAR) of 53.57. Furthermore, RT was associated with an increased risk of developing SPMs following a diagnosis of GAC. Nonetheless, regarding the impact of RT on SPMs in GC, the previous studies possessed certain limitations. Firstly, it did not account for the latency period of radiation exposure. Secondly, it omitted the consideration of the influence of early death on the occurrence of SPMs. RT does not significantly increase the likelihood of specific SPMs across all primary malignancies, and there have been instances of conflicting results from the same site in previous studies. To improve the scientific validity and rigor of this study, we drew on the experience of RT for other malignancies than stomach and analyzed the reasons for these discrepancies, including factors such as the definition of the SPMs in each study, the latency period chosen, the follow-up time, the statistical methods used, and the sample size of the cohort population. Given the relatively low prevalence of SPMs, we utilized data from 17 registries of the SEER database, incorporating a broader population to increase the confidence of our results. This difficulty arises from the challenge of distinguishing between primary and recurrent tumors in the residual stomach within the SEER database. Therefore, we opted to exclude patients with a second tumor in the remnant stomach. To reduce bias in this retrospective study and improve the analysis's robustness, we employed a 1:1 PSM method to pair populations according to predefined inclusion and exclusion criteria. Additionally, recognizing variations in the latency periods for radiation-induced hematological and solid tumors, we established two cohorts: one comprising patients with a minimum survival of 2 years and the other with a minimum survival of 5 years, aligning with the briefest latency period for the development of second hematological and solid tumors, respectively. The choice of statistical analysis methods has a significant impact on the interpretation of the results. We applied a variety of statistical methods, including Poisson regression and competing risks regression, to fully validate the results of the study. The results showed that both methods consistently indicated that RT does not increase the risk of secondary hematologic and solid malignancies. In addition, patients were categorized into subgroups based on clinical characteristics with the aim of accurately assessing potential RT risk. Our study has several limitations. First, being a population-based study, potential bias may arise due to the non-randomized allocation of the initial treatment, leading to an inability to eliminate bias resulting from imbalances between patients receiving and not receiving RT. Second, the absence of detailed data on postoperative RT modalities, dose, and frequency limited our exploration of the dose-response relationship between RT and SPMs development. Third, the occurrence of SPMs may not solely be associated with RT exposure but could also be influenced by other significant risk factors, such as lifestyle, genetic background, environmental factors, and other cancer-related treatments, which cloud be further elucidated in prospective cohort study or clinical trials. Conclusions In summary, despite the relatively low occurrence of radiotherapy-induced SPMs, their impact on patients could be significant. We conducted a pioneering exploratory study to comprehensively assess whether RT increases the risk of SPMs in patients with resectable GC using multiple methods. The findings indicate that RT not only failed to increase the risk of SPMs but also contributed to an improved prognosis for GC patients. Declarations Funding None. Acknowledgements None. Conflicts of Interest No potential conflict of interest relevant to this article was reported. References Sung H, Ferlay J, Siegel RL, et al. 2021. 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Zhu X, Zhou J, Zhou L, Zhang M, Gao C, Tao L. Association between postoperative radiotherapy for young-onset head and neck cancer and long-term risk of second primary malignancy: a population-based study. J Transl Med. 2022. 20(1): 405. Yi H, Li S, Lin Y, et al. Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer. J Gastroenterol Hepatol. 2023. 38(6): 930-939. Teng CJ, Huon LK, Hu YW, et al. Secondary Primary Malignancy Risk in Patients With Cervical Cancer in Taiwan: A Nationwide Population-Based Study. Medicine (Baltimore). 2015. 94(43): e1803. Shah BK, Khanal A, Hewett Y. Second Primary Malignancies in Adults with Gastric Cancer - A US Population-Based Study. Front Oncol. 2016. 6: 82. Jin L, Su X, Li W, Wu J, Zhang H. Incidence, risk and prognosis of second primary malignancy of patients with gastric adenocarcinoma. Sci Rep. 2024. 14(1): 5766. Additional Declarations No competing interests reported. Supplementary Files supplement.pdf supplement.docx Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 25 Jul, 2024 Submission checks completed at journal 25 Jul, 2024 First submitted to journal 16 Jul, 2024 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-4747305\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":331848901,\"identity\":\"7d691861-b915-4832-9487-2e45ed07fbbf\",\"order_by\":0,\"name\":\"Li Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Graduate School, Chinese PLA Medical School＆Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Li\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":331848902,\"identity\":\"85207c95-8177-49b0-a332-fb63dd2ccd2b\",\"order_by\":1,\"name\":\"Yunhe Gao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yunhe\",\"middleName\":\"\",\"lastName\":\"Gao\",\"suffix\":\"\"},{\"id\":331848903,\"identity\":\"92d2d0e3-1921-4f24-9439-c92fc7aaac14\",\"order_by\":2,\"name\":\"Hua Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Surgical Oncology, Affiliated Xing Tai People’s Hospital of Hebei Medial University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hua\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":331848904,\"identity\":\"5f74374f-e882-4752-af3e-2109bb4314af\",\"order_by\":3,\"name\":\"Benlong Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Benlong\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":331848905,\"identity\":\"91f5ff8f-1b92-48c4-9f19-a0eb4790508f\",\"order_by\":4,\"name\":\"Zijian Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zijian\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":331848906,\"identity\":\"40e41a22-7f1f-4cb6-a670-991d26161840\",\"order_by\":5,\"name\":\"ErPeng Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Second School of Clinical Medicine, Southern Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"ErPeng\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":331848907,\"identity\":\"e03d7d7a-3fe7-40b9-b00d-8a13887f7ee2\",\"order_by\":6,\"name\":\"Kecheng Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kecheng\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":331848908,\"identity\":\"a6284df9-e936-4ff9-b74e-3b5d3ef00c16\",\"order_by\":7,\"name\":\"Shaoyou Xia\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shaoyou\",\"middleName\":\"\",\"lastName\":\"Xia\",\"suffix\":\"\"},{\"id\":331848909,\"identity\":\"da929e36-e194-4e30-91fa-bd3251eebeaf\",\"order_by\":8,\"name\":\"Zhi Qiao\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYDCCA2DEkMDG3tj44ANpWngONxvOIFYLCCQwSKS3SXMQo4Pv9uGNB35U1OXxST5skGZgsJPTbSCgRfJcWsHBnjNsxWzSiQ3GBQzJxmYHCGgxOMNjcIC3jSexDagleQbDgcRtxGg5+LdNIrFN8mDDYR5itRzmbTNIbJNgbGwmSovkGbaCwzJnEhKBbmtmnGFAhF/4zjBv/vimoi5xfvvx5z8+VNjJEdQCchsONpFaRsEoGAWjYBRgAQBOK0bGxXmUKgAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Department of General Surgery, the First Medical Center, Chinese PLA General Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Zhi\",\"middleName\":\"\",\"lastName\":\"Qiao\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-07-16 05:57:43\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4747305/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4747305/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":63374415,\"identity\":\"1d18ac89-fd29-4ac2-909e-2946b503116e\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:24:39\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":456905,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eComparison of OS(A) and DSS(B) in patients with gastric cancer who were\\u003c/p\\u003e\\n\\u003cp\\u003etreated with RT and those who were not treated with RT\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/06fa7d103bbae95ca11c252c.png\"},{\"id\":63373355,\"identity\":\"00935435-55bd-4e31-9753-1332a6b7eb20\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:16:39\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":262622,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eComparison of the cumulative incidence of second primary hematological\\u003c/p\\u003e\\n\\u003cp\\u003emalignancies and solid malignancies in patients treated with RT and those who did not.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/a4ec546e8a6dc8d5b1b87ea1.png\"},{\"id\":63373357,\"identity\":\"fb05629d-5257-4b1e-b304-97983eb01459\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:16:39\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":886966,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSubgroup analyses of competing risk regression for\\u003c/p\\u003e\\n\\u003cp\\u003ethe risk of developing second hematologic malignancies.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/ee97ad1a4fca2f4ca87f19e5.png\"},{\"id\":63374945,\"identity\":\"6c1ccd0a-3c4d-4795-997d-9b716ac91fbf\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:32:40\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2455427,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/bd4c0ae8-fc00-4050-b664-a5cfb9d7a769.pdf\"},{\"id\":63373360,\"identity\":\"527e6bc5-3980-4797-9074-2371168710cb\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:16:40\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":699056,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplement.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/56560000fa79202765b82596.pdf\"},{\"id\":63373359,\"identity\":\"75ef0291-bebc-4998-aeed-ab6c615f0497\",\"added_by\":\"auto\",\"created_at\":\"2024-08-27 12:16:39\",\"extension\":\"docx\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":102357,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"supplement.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4747305/v1/4dcf781d308c4b20a375d940.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Association Between Radiotherapy and Non-Gastric Second Primary Malignancies in Patients with Resectable Gastric Cancer : A propensity-adjusted, population-based SEER analysis\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eGastric cancer (GC) is one of the most prevalent malignancies and stands as one of the top four contributors to tumor-related fatalities worldwide\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e. While curative gastrectomy and regional lymph node dissection (LND) are recognized as crucial for the standardized management of resectable GC, a significant proportion of patients still experience recurrence, resulting in unfavorable prognoses\\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e. Therefore, in effort to improve the limited survival rates among patients afflicted with this condition, multimodal adjuvant therapeutic strategies have undergone thorough examination and received widespread approval\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR5\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]\\u003c/sup\\u003e. More precisely, the incorporation of perioperative chemotherapy or radiotherapy has been found to significantly optimize surgical outcomes\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR8\\\" citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e. However, the role of radiotherapy (RT) alone in the improvement of the prognosis of GC has recently been questioned\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR11\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e. Given this backdrop, the potential side effects of RT become paramount in decision-making, necessitating a careful assessment of the advantages and disadvantages of RT.\\u003c/p\\u003e \\u003cp\\u003eThe occurrence of second primary malignancies (SPMs), which are tumors that develop independently after an initial malignancy and are not the result of metastasis or recurrence, can have a significant impact on the quality of life and long-term survival prospects of patients with GC. Recent studies have demonstrated that RT notably increases the likelihood of developing SPMs across various cancer types, including rectal\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR14\\\" citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]\\u003c/sup\\u003e, breast\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR17 CR18\\\" citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]\\u003c/sup\\u003e, and lung cancer\\u003csup\\u003e[\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]\\u003c/sup\\u003e. The occurrence of SPMs associated with RT, though infrequent, is a late-emerging complication that warrants attention. However, there have been limited studies concerning whether RT for GC poses an elevated risk for the development of SPMs.\\u003c/p\\u003e \\u003cp\\u003eThis study employed various methods to evaluate the risk of radiotherapy-associated SPMs and analyze its impact on the prognosis of resectable GC, using the Surveillance, Epidemiology, and End Results (SEER) database. This aspect, infrequently addressed in prior studies, holds significance for guiding the selection of RT for GC.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eParticipant cohorts and cohort definition\\u003c/h2\\u003e \\u003cp\\u003eThe SEER database comprises publicly accessible and anonymized data, thereby eliminating the necessity for patient consent or institutional review board approval(Human Ethics and Consent to Participate declarations: not applicable). Throughout its entirety, the study adhered strictly to the Strengthening Reporting Guidelines for Observational Studies in Epidemiology(STROBE)\\u003csup\\u003e[\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThis study utilized data from 17 registries in the SEER database, covering patients diagnosed with GC as the first primary cancer between January 2000, and December 2020. Patient diagnoses were pathologically confirmed and coded according to the ICD-O-3 site codes (C16.9). The tumor staging for the included individuals was confined to localized and regional stages, and all of them were undergoing surgical treatment. Exclusion criteria included age less than 20 years or more than 85 years, patients with distant metastases, other types of gastric tumors (gastric mesenchymal tumors, gastric neuroendocrine tumors), other RT regimens, significant missing information, e.g. clinical characteristics, treatment strategies or survival information, mainly including age at gastric cancer diagnosis, race, tumor stage, radiation therapy, year of diagnosis, chemotherapy, survival time, and survival status, etc. Following the prescribed treatment protocol, patients were categorized into two groups: the radiotherapy (RT) group, including GC patients who underwent surgery and perioperative external beam radiotherapy, and a non-radiotherapy (NRT) group, comprising GC patients who underwent surgery only.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eOutcome and Follow-up\\u003c/h2\\u003e \\u003cp\\u003eThe primary outcome of this study was defined as the occurrence of second primary malignancies (SPMs), including either second hematologic malignancies or second solid malignancies, at two or five years post-diagnosis of the initial malignancy, respectively. The determination of the cutoff for survival time was based on the minimum latency period observed for radiation-induced tumorigenesis\\u003csup\\u003e[\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]\\u003c/sup\\u003e. To comprehensively evaluate the risk of SPMs development, we initially examined the risk of all second hematological or solid malignancies. Subsequently, we classified specific tumors based on their site and organ system to estimate the risk of distinct types of SPMs. Apart from the primary endpoint of SPMs, overall survival (OS) and disease-specific survival (DSS) were designated as secondary outcomes. OS refers to the duration commencing from the GC diagnosis until demise due to any cause, whereas DSS denotes the elapsed time from GC diagnosis until death solely attributed to the primary malignancy.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eContinuous variables were represented as medians along with interquartile ranges (IQR), and analyzed using the Mann-Whitney U test. Categorical variables were described in frequencies and percentages, and their analysis employed either the χ\\u003csup\\u003e2\\u003c/sup\\u003e or Fisher\\u0026rsquo;s exact test. Propensity score matching(PSM) with a caliper width of 0.01 was employed to achieve a 1:1 ratio matching of the two groups, with the objective of minimizing potential bias in the comparison of second primary tumor incidence and prognosis. To assess the prognosis of RT in GC patients, we utilized the Kaplan-Meier method for survival curve generation and conducted a log-rank test to derive the corresponding P-values. Furthermore, a comprehensive evaluation of RT's influence on prognosis was carried out through variable screening and confounder control, employing both univariate and multivariate survival analyses.\\u003c/p\\u003e \\u003cp\\u003eFine-Gray competing risk regression analysis was employed to assess the cumulative incidence of SPMs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of SPMs were calculated, considering all-cause death as competing events. Through subgroup analysis of competing risks, we attempted to identify the population potentially affected by radiation therapy, and the results are presented in a forest plot. Additionally, we conducted Poisson regression analyses to assess the relative risks (RRs) and 95% CIs of SPMs in GC patients who underwent RT, in comparison to those who did not. To further assess the dynamic risk of SPMs associated with RT, we estimated the risk based on latency since diagnosis, age at diagnosis, and year of diagnosis, stratifying the RRs. Statistical analysis was conducted using R software (version 4.2.2). A two-tailed p-value of \\u0026lt;\\u0026thinsp;0.05 was considered as indicative of statistical significance.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec7\\\"\\u003e\\n \\u003ch2\\u003ePatient Characteristics\\u003c/h2\\u003e\\n \\u003cp\\u003eInitially, a total of 37,487 GC patients were identified. Following stringent inclusion and exclusion criteria, the final cohort included 24,390 patients in the study (eFigure 1), in which the median age was 67 years (IQR, 57\\u0026ndash;75 years). Among them, 15,619 patients (64.0%) were male. Additionally, 15,878 patients (65.1%) were in the NRT group, while 8,512 patients (34.9%) were in the RT group. The baseline characteristics of the treatment modalities of GC patients are detailed in eTable 1. Following the 1:1 PSM, a total of 7113 patients were included in both the RT and NRT groups. These patients exhibited balanced and comparable baseline characteristics, as detailed in eTable 2.\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec8\\\"\\u003e\\n \\u003ch2\\u003eSurvival Outcome\\u003c/h2\\u003e\\n \\u003cp\\u003eThe findings revealed that patients receiving RT had a median OS of 38 months and a DSS of 47 months. The 3-year OS and DSS rates were 51.4% and 55.6%, respectively, while the 5-year rates were 40.4% and 46.3%. In contrast, patients in the NRT group had a median OS of 25 months and a DSS of 32 months. The 3-year OS and DSS rates were 41.6% and 47.4%, while five-year rates were 32.8% and 39.9%. The difference in OS and DSS between the two groups was statistically significant (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001), as shown in Fig.\\u0026nbsp;1. Furthermore, survival analysis indicated that RT played an active role in the treatment of GC and significantly improved OS and DSS of patients, as shown in eTable 3 and eTable 4.\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec9\\\"\\u003e\\n \\u003ch2\\u003eCumulative Incidences of SPMs\\u003c/h2\\u003e\\n \\u003cp\\u003eFollowing a 2-year latency, second hematologic malignancies manifested in 31 (0.70%) patients in the RT group and 25 (0.70%) patients in the NRT group, as detailed in Table\\u0026nbsp;\\u003cspan\\u003e1\\u003c/span\\u003e and eTable 5. After a latency period of 5 years, second solid malignancies occurred in 209 (7.40%) patients in the RT group and 134 (6.80%) patients in the NRT group. The baseline characteristics of patients developing second solid malignancies are displayed in Table\\u0026nbsp;\\u003cspan\\u003e2\\u003c/span\\u003e and eTable 6.\\u003c/p\\u003e\\n \\u003cdiv\\u003e\\n \\u003ctable id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv\\u003eTable 1\\u003c/div\\u003e\\n \\u003cdiv\\u003e\\n \\u003cp\\u003eComparisons of characteristics of different treatment modalities in patients with gastric cancer after PSM and surviving more than 2 years.\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003ccolgroup cols=\\\"4\\\"\\u003e\\u003c/colgroup\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eCharacteristic\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNRT, no. (%)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRT, no. (%)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;3577)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;4483)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSex\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.279\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFemale\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1152 (32.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1496 (33.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMale\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2425 (67.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2987 (66.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAge at GC diagnosis, yrs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.025\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e20\\u0026ndash;49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e617 (17.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e673 (15.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e50\\u0026ndash;69\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2001 (55.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2571 (57.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e70\\u0026ndash;84\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e959 (26.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1239 (27.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRace\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.363\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eWhite\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2404 (67.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2950 (65.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eBlack\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e411 (11.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e552 (12.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eOther\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e762 (21.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e981 (21.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCalendar year of GC diagnosis\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.118\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2000\\u0026ndash;2004\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1114 (31.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1426 (31.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2005\\u0026ndash;2009\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1062 (29.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1399 (31.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2010\\u0026ndash;2015\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1401 (39.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1658 (37.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor location\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.014\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eEsophagogastric junction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1182 (33.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1366 (30.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eStomach\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2395 (67.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e3117 (69.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eLocalized\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1011 (28.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e950 (21.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRegional\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2566 (71.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e3533 (78.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor grade\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eGrade I/II\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1231 (34.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1322 (29.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eGrade III/IV\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2109 (59.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2962 (66.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eUnknown\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e237 (6.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e199 (4.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor size, cm\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;2.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e559 (15.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e341 (7.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2.0-4.9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1332 (37.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1816 (40.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026gt;\\u0026thinsp;5.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1201 (33.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1751 (39.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eUnknown\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e485 (13.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e575 (12.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor histology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAdenocarcinoma\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2678 (74.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e3308 (73.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMucous tumor\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e772 (21.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1087 (24.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eOthers\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e127 (3.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e88 (2.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eChemotherapy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNo\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2176 (60.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e268 (6.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eYes\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1401 (39.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e4215 (94.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSecond hematologic malignancies\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e25 (0.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e31 (0.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eLatency, mo, median (IQR)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e72.0 (48.0-116.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e73.0 (52.0-136.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.680\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSurvival.monthsr, mo, median (IQR)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e77 (42\\u0026ndash;130)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e80 (42\\u0026ndash;135)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.053\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNOTE:\\u003c/strong\\u003e P values were calculated using \\u0026chi;2 test (a) for categorical variables and the Mann-Whitney U test (b) for continuous variables of skewed distributions.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAbbreviations:\\u003c/strong\\u003e PSM, propensity score matching; RT, radiation therapy; NRT, no radiation therapy; GC, gastric cancer; yrs, years old; IQR, interquartile range.\\u003c/p\\u003e\\n \\u003cdiv\\u003e\\n \\u003ctable id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv\\u003eTable 2\\u003c/div\\u003e\\n \\u003cdiv\\u003e\\n \\u003cp\\u003eComparisons of characteristics of different treatment modalities in patients with gastric cancer after PSM surviving more than 5 years.\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003ccolgroup cols=\\\"4\\\"\\u003e\\u003c/colgroup\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eCharacteristic\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNRT, no. (%)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRT, no. (%)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;2259)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;2814)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSex\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.159\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFemale\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e714 (31.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e943 (33.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMale\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1545 (68.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1871 (66.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAge at GC diagnosis, yrs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.032\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e20\\u0026ndash;49\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e414 (18.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e438 (15.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e50\\u0026ndash;69\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1288 (57.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1652 (58.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e70\\u0026ndash;84\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e557 (24.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e724 (25.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRace\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.097\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eWhite\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1503 (66.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1791 (63.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eBlack\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e264 (11.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e351 (12.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eOther\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e492 (21.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e672 (23.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCalendar year of GC diagnosis\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.011\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2000\\u0026ndash;2004\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e698 (30.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e899 (31.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2005\\u0026ndash;2009\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e659 (29.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e902 (32.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2010\\u0026ndash;2015\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e902 (39.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1013 (36.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor location\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eEsophagogastric junction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e753 (33.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e794 (28.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eStomach\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1506 (66.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2020 (71.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eLocalized\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e816 (36.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e688 (24.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRegional\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1443 (63.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2126 (75.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor grade\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eGrade I/II\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e845 (37.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e864 (30.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eGrade III/IV\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1246 (55.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1820 (64.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eUnknown\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e168 (7.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e130 (4.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor size, cm\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;2.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e452 (20.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e242 (8.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2.0-4.9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e850 (37.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1177 (41.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026gt;\\u0026thinsp;5.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e660 (29.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1058 (37.6%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eUnknown\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e297 (13.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e337 (12.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eTumor histology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAdenocarcinoma\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1729 (76.5%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2107 (74.9%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMucous tumor\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e436 (19.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e650 (23.1%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eOthers\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e94 (4.2%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e57 (2.0%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eChemotherapy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNo\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e1452 (64.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e176 (6.3%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eYes\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e807 (35.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2638 (93.7%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSecond solid malignancies\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e153 (6.8%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e209 (7.4%)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.398\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eLatency, mo, median (IQR)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e98.0 (72.0-131.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e102.0 (78.0-138.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.210\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSurvival.monthsr, mo, median (IQR)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e114 (81\\u0026ndash;162)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e119 (86\\u0026ndash;165)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.005\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNOTE:\\u003c/strong\\u003e P values were calculated using \\u0026chi;2 test (a) for categorical variables and the Mann-Whitney U test (b) for continuous variables of skewed distributions.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAbbreviations:\\u003c/strong\\u003e PSM, propensity score matching; RT, radiation therapy; NRT, no radiation therapy; GC, gastric cancer; yrs, years old; IQR, interquartile range.\\u003c/p\\u003e\\n \\u003cp\\u003eTwo years after a GC diagnosis, the cumulative incidence of hematologic malignancies was 0.70%. Notably, hematologic malignancies showed a cumulative incidence of 0.70% among RT-receiving patients, contrasting with 0.70% among those without RT (P\\u0026thinsp;=\\u0026thinsp;0.868, refer to Fig.\\u0026nbsp;2). The cumulative incidence of malignancies for solid tumors was 7.14%. In the RT group, this value was 7.43%, while patients without RT exhibited a cumulative incidence of 6.77% for second solid malignancies (P\\u0026thinsp;=\\u0026thinsp;0.618, see Figure. 2). In location-specific analysis, no statistically significant difference was observed in the cumulative incidence rate of major solid tumors between the RT and NRT groups (P\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05, eFigure 2).\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec10\\\"\\u003e\\n \\u003ch2\\u003eCorrelation of Radiotherapy with SPMs\\u003c/h2\\u003e\\n \\u003cp\\u003eUnivariate competing risks regression analysis was conducted, encompassing all variables listed in eTable 7 and eTable 8. Inclusion of statistically significant variables in univariate analysis, as well as the RT in the multivariate analysis. The results indicated that the incidence of second primary hematological or solid malignancies was not linked to RT (HR\\u0026thinsp;=\\u0026thinsp;0.96, 95% CI, 0.57\\u0026ndash;1.62, P\\u0026thinsp;=\\u0026thinsp;0.87; HR\\u0026thinsp;=\\u0026thinsp;1.05, 95% CI, 0.86\\u0026ndash;1.30, P\\u0026thinsp;=\\u0026thinsp;0.61). In the subgroup stratified by clinicopathological features, RT was not associated with the development of SPMs, as shown in Fig.\\u0026nbsp;3 and eFigure 3 (eTable 9 and eTable 10). In Poisson regression analysis, the adjusted RR was computed to verify the association between the risk of SPMs and RT, taking into account the modifying effects of patient age, sex, and the calendar year at the time of GC diagnosis. The adjusted RR for the additional risk of combined second primary hematological malignancies was found to be 1.04 (95% CI, 0.61\\u0026ndash;1.78, P\\u0026thinsp;=\\u0026thinsp;0.89), with the adjusted RR of second primary solid malignancies ( RR\\u0026thinsp;=\\u0026thinsp;1.09, 95% CI, 0.88\\u0026ndash;1.34, P\\u0026thinsp;=\\u0026thinsp;0.44) (Table\\u0026nbsp;\\u003cspan\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\n \\u003cdiv\\u003e\\n \\u003ctable id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption language=\\\"En\\\"\\u003e\\n \\u003cdiv\\u003eTable 3\\u003c/div\\u003e\\n \\u003cdiv\\u003e\\n \\u003cp\\u003eStatistical analysis of the risk of development of SPMs in patients with gastric cancer\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003ccolgroup cols=\\\"9\\\"\\u003e\\u003c/colgroup\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eVariables\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eMultivariable Competing Risk Regression (RT vs NRT)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003ePoisson regression\\u003c/p\\u003e\\n \\u003cp\\u003e(RT vs NRT)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\" colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003ePoisson regression\\u003c/p\\u003e\\n \\u003cp\\u003e(RT vs NRT)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eHR (95% CI)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRR (95% CI)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAdjusted RR (95% CI)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSecondary hematologic malignancies\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.96(0.57\\u0026ndash;1.62)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.87\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.99(0.59\\u0026ndash;1.69)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.97\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.04(0.61\\u0026ndash;1.78)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.89\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSecondary solid malignancies\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.05(0.86\\u0026ndash;1.30)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.61\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.10(0.89\\u0026ndash;1.35)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.39\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.09(0.88\\u0026ndash;1.34)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.44\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNOTE:\\u003c/strong\\u003e Fine-Gray competing risk regression analyses were conducted to ascertain the HR and 95% CI for SPMs in GC patients undergoing RT, in contrast to those who did not. The variable pertaining to RT, along with statistically significant covariates identified via univariate competing risks regression analyses (P \\u0026lt; 0.05), were subsequently incorporated into the multivariate analysis. Poisson regression analysis was used to assess the RR and 95%CI of SPMs in patients who underwent RT vs. those who did not. Similarly, in the calculation of RRs as well as 95% CIs for patients with RT and NRT from Poisson regression analyses, we have adjusted for age, sex, and the calendar year at the time of GC diagnosis.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAbbreviations:\\u003c/strong\\u003e SPMs, second primary malignancies; GC, gastric cancer; RT, radiation therapy; NRT, no radiation therapy; HR, hazard ratio; RR, radiotherapy-associated risk.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec11\\\"\\u003e\\n \\u003ch2\\u003eDynamic Risk Evaluation for SPMs\\u003c/h2\\u003e\\n \\u003cp\\u003eAfter in-depth analysis of three dynamic RR plots for age at GC diagnosis, year of diagnosis, and latency, we observed that RT did not significantly increase the risk of SPMs at any stage. However, the trends for second primary haematological and second primary solid malignancies showed some variability. In the dynamic age-adjusted RR plot, the risk of developing a second primary solid malignancies in GC patients receiving RT, as depicted in Fig.\\u0026nbsp;5 (20\\u0026ndash;49 year-old: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.13, 95% CI 0.59\\u0026ndash;2.16, P\\u0026thinsp;=\\u0026thinsp;0.717; 50\\u0026ndash;69 year-old: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.01, 95% CI 0.78\\u0026ndash;1.32, P\\u0026thinsp;=\\u0026thinsp;0.917; 70\\u0026ndash;84 year-old: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.17, 95% CI 0.76\\u0026ndash;1.85, P\\u0026thinsp;=\\u0026thinsp;0.483). However, the risk of haematological malignancies in the 20\\u0026ndash;49 age group could not be accurately assessed due to sample size limitations. RR plot for second primary haematological malignancies in other age groups is in Fig.\\u0026nbsp;5 (50\\u0026ndash;69 year-old: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.86, 95% CI 0.47\\u0026ndash;1.86, P\\u0026thinsp;=\\u0026thinsp;0.838; 70\\u0026ndash;84 year-old: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.24, 95% CI 0.52\\u0026ndash;3.17, P\\u0026thinsp;=\\u0026thinsp;0.631). Analysis of dynamic year of diagnosis-adjusted RR plot shows that second primary haematological malignancies differ from solid malignancies in their trends. The risk of haematological malignancies appears to decrease gradually over years. However, the risk of developing a second primary malignancy in patients treated with RT varies with the calendar years since diagnosis (2000\\u0026ndash;2004: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.63, 95% CI 0.68\\u0026ndash;4.32, P\\u0026thinsp;=\\u0026thinsp;0.290; 2005\\u0026ndash;2009: adjusted RR\\u0026thinsp;=\\u0026thinsp;1.18, 95% CI 0.51\\u0026ndash;2.85, P\\u0026thinsp;=\\u0026thinsp;0.711; 2010\\u0026ndash;2015: adjusted RR\\u0026thinsp;=\\u0026thinsp;0.40, 95% CI 0.12\\u0026ndash;1.32, P\\u0026thinsp;=\\u0026thinsp;0.134). In the dynamic latency-RR plot, no significant changes were observed for haematological and solid malignancies with latency. In addition, the RR results of the SPMs in patients treated with RT was similar to the adjusted RR plots (eFigures 4, eTable 11 and eTable 12 in the Supplementary Appendix).\\u003c/p\\u003e\\n\\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eRadiotherapy is a crucial component of the comprehensive treatment for GC, contributing significantly to overall treatment outcomes\\u003csup\\u003e[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]\\u003c/sup\\u003e. However, the potential toxic effects of RT on patients should not be ignored, especially the radiation exposure associated with RT may lead to the development of SPMs, an easily overlooked complication. Despite advancements in RT techniques mitigating inadvertent irradiation of adjacent normal tissues, some studies\\u003csup\\u003e[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]\\u003c/sup\\u003e indicate an increased risk of SPMs after RT for specific cancers. In this study, leveraging data from a substantial population-based cohort, we employed various methods to unravel the intricate relationship between RT and individual SPMs risk in resectable GC patients, simultaneously evaluating the prognostic impact of RT on primary GC patients. Our findings indicate that RT not only does not increase the risk of developing second primary hematologic or solid malignancies in GC patients but also improves OS and DSS in these individuals.\\u003c/p\\u003e \\u003cp\\u003eRT is widely acknowledged as a significant risk factor for specific SPMs across various primary cancer types. For instance, in a study by Guan et al\\u003csup\\u003e[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]\\u003c/sup\\u003e, involving 20,142 female patients with rectal cancer as the first primary cancer who survived for at least 5 years, various ways of statistical analysis revealed a significant increase in the risk of uterine corpus and ovarian cancer following RT. On a different note, Zhou et al\\u003csup\\u003e[\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]\\u003c/sup\\u003e. analyzed 62,435 patients with nonmetastatic lung cancer who underwent surgery, demonstrating a significant association between RT and an increased risk of major second primary malignant tumors (RR\\u0026thinsp;=\\u0026thinsp;1.21; 95% CI, 1.08\\u0026ndash;1.35), particularly in the development of second primary gastrointestinal malignancies (RR\\u0026thinsp;=\\u0026thinsp;1,77, 95%CI: 1.44\\u0026ndash;2.15). Conversely, there was no association with the development of second hematologic malignancies (RR\\u0026thinsp;=\\u0026thinsp;1.08, 95% CI: 0.84\\u0026ndash;1.37).\\u003c/p\\u003e \\u003cp\\u003eIn the context of the SPMs in GC, Chen et al\\u003csup\\u003e[\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]\\u003c/sup\\u003e. identified RT as an independent risk factor for SPMs in a study involving 137,798 participants from the Taiwan National Health Insurance database. Binay et al\\u003csup\\u003e[\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]\\u003c/sup\\u003e. conducted an evaluation of 33,720 patients drawn from the SEER 13 database, employing standardized incidence rate ratios (SIRs). Their research has demonstrated a significantly elevated risk of developing SPMs among GC patients in the United States, when compared to the general population. Additionally, the research highlighted a noteworthy increase in SPMs risk during RT for GC. Similarly, Jin et al\\u003csup\\u003e[\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]\\u003c/sup\\u003e. analyzed data on patients diagnosed with gastric adenocarcinoma (GAC) in the SEER database from 2000 to 2020. The results showed that patients with GAC had a significantly increased risk of developing SPMs, with a SIRs of 1.36, 95% CI of 1.32\\u0026ndash;1.40 and an excess incidence risk (EAR) of 53.57. Furthermore, RT was associated with an increased risk of developing SPMs following a diagnosis of GAC. Nonetheless, regarding the impact of RT on SPMs in GC, the previous studies possessed certain limitations. Firstly, it did not account for the latency period of radiation exposure. Secondly, it omitted the consideration of the influence of early death on the occurrence of SPMs.\\u003c/p\\u003e \\u003cp\\u003eRT does not significantly increase the likelihood of specific SPMs across all primary malignancies, and there have been instances of conflicting results from the same site in previous studies. To improve the scientific validity and rigor of this study, we drew on the experience of RT for other malignancies than stomach and analyzed the reasons for these discrepancies, including factors such as the definition of the SPMs in each study, the latency period chosen, the follow-up time, the statistical methods used, and the sample size of the cohort population. Given the relatively low prevalence of SPMs, we utilized data from 17 registries of the SEER database, incorporating a broader population to increase the confidence of our results. This difficulty arises from the challenge of distinguishing between primary and recurrent tumors in the residual stomach within the SEER database. Therefore, we opted to exclude patients with a second tumor in the remnant stomach. To reduce bias in this retrospective study and improve the analysis's robustness, we employed a 1:1 PSM method to pair populations according to predefined inclusion and exclusion criteria. Additionally, recognizing variations in the latency periods for radiation-induced hematological and solid tumors, we established two cohorts: one comprising patients with a minimum survival of 2 years and the other with a minimum survival of 5 years, aligning with the briefest latency period for the development of second hematological and solid tumors, respectively. The choice of statistical analysis methods has a significant impact on the interpretation of the results. We applied a variety of statistical methods, including Poisson regression and competing risks regression, to fully validate the results of the study. The results showed that both methods consistently indicated that RT does not increase the risk of secondary hematologic and solid malignancies. In addition, patients were categorized into subgroups based on clinical characteristics with the aim of accurately assessing potential RT risk.\\u003c/p\\u003e \\u003cp\\u003eOur study has several limitations. First, being a population-based study, potential bias may arise due to the non-randomized allocation of the initial treatment, leading to an inability to eliminate bias resulting from imbalances between patients receiving and not receiving RT. Second, the absence of detailed data on postoperative RT modalities, dose, and frequency limited our exploration of the dose-response relationship between RT and SPMs development. Third, the occurrence of SPMs may not solely be associated with RT exposure but could also be influenced by other significant risk factors, such as lifestyle, genetic background, environmental factors, and other cancer-related treatments, which cloud be further elucidated in prospective cohort study or clinical trials.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eIn summary, despite the relatively low occurrence of radiotherapy-induced SPMs, their impact on patients could be significant. We conducted a pioneering exploratory study to comprehensively assess whether RT increases the risk of SPMs in patients with resectable GC using multiple methods. The findings indicate that RT not only failed to increase the risk of SPMs but also contributed to an improved prognosis for GC patients.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNone.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNone.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflicts of Interest\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo potential conflict of interest relevant to this article was reported.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eSung H, Ferlay J, Siegel RL, et al. 2021. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 71(3): 209-249.\\u003c/li\\u003e\\n\\u003cli\\u003eYoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000. 87(2): 236-42.\\u003c/li\\u003e\\n\\u003cli\\u003eD\\u0026apos;Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004. 240(5): 808-16.\\u003c/li\\u003e\\n\\u003cli\\u003eLim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005. 23(25): 6220-32.\\u003c/li\\u003e\\n\\u003cli\\u003eAbraham I, Dhar P, Praseedom RK. Adjuvant chemoradiotherapy for gastric cancer. N Engl J Med. 2002. 346(3): 210-1.\\u003c/li\\u003e\\n\\u003cli\\u003eAllen CJ, Pointer DT Jr, Blumenthaler AN, et al. Chemotherapy Versus Chemotherapy Plus Chemoradiation as Neoadjuvant Therapy for Resectable Gastric Adenocarcinoma: A Multi-institutional Analysis. Ann Surg. 2021. 274(4): 544-548.\\u003c/li\\u003e\\n\\u003cli\\u003eCunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006. 355(1): 11-20.\\u003c/li\\u003e\\n\\u003cli\\u003eMacdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001. 345(10): 725-30.\\u003c/li\\u003e\\n\\u003cli\\u003eMokdad AA, Yopp AC, Polanco PM, et al. Adjuvant Chemotherapy vs Postoperative Observation Following Preoperative Chemoradiotherapy and Resection in Gastroesophageal Cancer: A Propensity Score-Matched Analysis. JAMA Oncol. 2018. 4(1): 31-38.\\u003c/li\\u003e\\n\\u003cli\\u003eCats A, Jansen E, van Grieken N, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018. 19(5): 616-628.\\u003c/li\\u003e\\n\\u003cli\\u003ede Steur WO, van Amelsfoort RM, Hartgrink HH, et al. Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial. Ann Oncol. 2021. 32(3): 360-367.\\u003c/li\\u003e\\n\\u003cli\\u003eLordick F, Nilsson M, Leong T. Adjuvant radiotherapy for gastric cancer-end of the road. Ann Oncol. 2021. 32(3): 287-289.\\u003c/li\\u003e\\n\\u003cli\\u003eGuan X, Wei R, Yang R, et al. Association of Radiotherapy for Rectal Cancer and Second Gynecological Malignant Neoplasms. JAMA Netw Open. 2021. 4(1): e2031661.\\u003c/li\\u003e\\n\\u003cli\\u003eRombouts A, Hugen N, Elferink M, et al. Incidence of second tumors after treatment with or without radiation for rectal cancer. Ann Oncol. 2017. 28(3): 535-540.\\u003c/li\\u003e\\n\\u003cli\\u003eMoschini M, Zaffuto E, Karakiewicz PI, et al. External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis. Eur Urol. 2019. 75(2): 319-328.\\u003c/li\\u003e\\n\\u003cli\\u003eGrantzau T, Overgaard J. Risk of second non-breast cancer among patients treated with and without postoperative radiotherapy for primary breast cancer: A systematic review and meta-analysis of population-based studies including 522,739 patients. Radiother Oncol. 2016. 121(3): 402-413.\\u003c/li\\u003e\\n\\u003cli\\u003eXia C, Qin L, Wang Y, Yao L, Shia B, Wu SY. Risk factors and specific cancer types of second primary malignancies in patients with breast cancer receiving adjuvant radiotherapy: a case-control cohort study based on the SEER database. Am J Cancer Res. 2022. 12(6): 2744-2756.\\u003c/li\\u003e\\n\\u003cli\\u003eRamin C, Veiga L, Vo JB, et al. Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort. Breast Cancer Res. 2023. 25(1): 50.\\u003c/li\\u003e\\n\\u003cli\\u003eHamilton SN, Tyldesley S, Li D, Olson R, McBride M. Second malignancies after adjuvant radiation therapy for early stage breast cancer: is there increased risk with addition of regional radiation to local radiation. Int J Radiat Oncol Biol Phys. 2015. 91(5): 977-85.\\u003c/li\\u003e\\n\\u003cli\\u003eZhou B, Zang R, Song P, et al. Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer: a population-based study. J Transl Med. 2023. 21(1): 10.\\u003c/li\\u003e\\n\\u003cli\\u003eHuang YJ, Huang TW, Lin FH, Chung CH, Tsao CH, Chien WC. Radiation Therapy for Invasive Breast Cancer Increases the Risk of Second Primary Lung Cancer: A Nationwide Population-Based Cohort Analysis. J Thorac Oncol. 2017. 12(5): 782-790.\\u003c/li\\u003e\\n\\u003cli\\u003evon Elm E, Altman DG, Egger M, Pocock SJ, G\\u0026oslash;tzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007. 370(9596): 1453-7.\\u003c/li\\u003e\\n\\u003cli\\u003eRoyal HD. Effects of low level radiation-what\\u0026apos;s new. Semin Nucl Med. 2008. 38(5): 392-402.\\u003c/li\\u003e\\n\\u003cli\\u003eLi R, Hou WH, Chao J, et al. Chemoradiation Improves Survival Compared With Chemotherapy Alone in Unresected Nonmetastatic Gastric Cancer. J Natl Compr Canc Netw. 2018. 16(8): 950-958.\\u003c/li\\u003e\\n\\u003cli\\u003eZhu X, Zhou J, Zhou L, Zhang M, Gao C, Tao L. Association between postoperative radiotherapy for young-onset head and neck cancer and long-term risk of second primary malignancy: a population-based study. J Transl Med. 2022. 20(1): 405.\\u003c/li\\u003e\\n\\u003cli\\u003eYi H, Li S, Lin Y, et al. Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer. J Gastroenterol Hepatol. 2023. 38(6): 930-939.\\u003c/li\\u003e\\n\\u003cli\\u003eTeng CJ, Huon LK, Hu YW, et al. Secondary Primary Malignancy Risk in Patients With Cervical Cancer in Taiwan: A Nationwide Population-Based Study. Medicine (Baltimore). 2015. 94(43): e1803.\\u003c/li\\u003e\\n\\u003cli\\u003eShah BK, Khanal A, Hewett Y. Second Primary Malignancies in Adults with Gastric Cancer - A US Population-Based Study. Front Oncol. 2016. 6: 82.\\u003c/li\\u003e\\n\\u003cli\\u003eJin L, Su X, Li W, Wu J, Zhang H. Incidence, risk and prognosis of second primary malignancy of patients with gastric adenocarcinoma. Sci Rep. 2024. 14(1): 5766.\\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\":\"info@researchsquare.com\",\"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\":\"Stomach neoplasms, Second primary malignancies, Radiotherapy, Surveillance, Epidemiology, and End Results (SEER)\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4747305/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4747305/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eThe study aims to investigate the relationship between radiotherapy (RT) and the risk of second primary malignancies (SPMs) in GC patients, and assess the prognostic impact of RT.\\u003c/p\\u003e\\u003ch2\\u003ePatients and methods:\\u003c/h2\\u003e \\u003cp\\u003eWe retrieved data on patients with primary GC from the SEER database. The study focused on the association between RT and the occurrence of hematologic malignancies at least 2 years post-diagnosis, as well as the emergence of solid cancers at least 5 years post-diagnosis. For the analysis, we employed competing risk regression analysis and Poisson regression following propensity score matching, along with implemented stratified analysis. Furthermore, we evaluated the impact of RT on the prognosis of GC patients using Kaplan-Meier and Cox regression analysis.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eA total of 24,390 surgically treated patients with pathologically confirmed GC were enrolled in the study. The median OS was 37.0 months (95%CI 16.0-100.0) in the RT group and 24.0 months (IQR, 8.0\\u0026ndash;24.0) in the NRT group (HR\\u0026thinsp;=\\u0026thinsp;0.77, 95%CI 0.74\\u0026ndash;0.80, P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). Among the survivors who lived beyond 2 years, 56 (0.70%) were diagnosed with second hematologic malignancies. Additionally, both competing risks and Poisson regressions indicate that RT is not linked to second hematologic malignancies (HR\\u0026thinsp;=\\u0026thinsp;0.96, 95%CI: 0.57\\u0026ndash;1.62, P\\u0026thinsp;=\\u0026thinsp;0.87; RR\\u0026thinsp;=\\u0026thinsp;0.99, 95%CI: 0.59\\u0026ndash;1.69, P\\u0026thinsp;=\\u0026thinsp;0.97). In 5-year survivors, 362 (7.10%) were diagnosed with second primary solid malignancies, and RT was also not associated with overall second solid malignancies (HR\\u0026thinsp;=\\u0026thinsp;1.05, 95%CI, 0.86\\u0026ndash;1.32, P\\u0026thinsp;=\\u0026thinsp;0.61; RR\\u0026thinsp;=\\u0026thinsp;1.10, 95%CI, 0.89\\u0026ndash;1.35, P\\u0026thinsp;=\\u0026thinsp;0.39). In subgroup analyses, no association was found between RT and SPM occurrence at any site, and no specific population was identified regarding the effect of RT on the development of SPMs.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eRT improves the prognosis for patients with resectable GC, with no evidence of increasing the risk of developing second primary hematologic or solid malignancies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Association Between Radiotherapy and Non-Gastric Second Primary Malignancies in Patients with Resectable Gastric Cancer : A propensity-adjusted, population-based SEER analysis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-08-27 12:16:34\",\"doi\":\"10.21203/rs.3.rs-4747305/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-07-25T17:57:56+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-07-25T05:55:10+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Cancer\",\"date\":\"2024-07-16T05:56:26+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"30b4b583-7657-4777-8b15-bd9db5ac8adb\",\"owner\":[],\"postedDate\":\"August 27th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-08-27T12:16:34+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-08-27 12:16:34\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4747305\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4747305\",\"identity\":\"rs-4747305\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}