Prognostic Factors Analysis in Breast Cancer Patients with Brain Metastases: Identification of Key Determinants of Survival1

Prognostic Factors Analysis in Breast Cancer Patients with Brain Metastases: Identification of Key Determinants of Survival1 | 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 Prognostic Factors Analysis in Breast Cancer Patients with Brain Metastases: Identification of Key Determinants of Survival1 Man Li, yuchen Ge, tao Wei, yifan Lei, yunyan Yang, mingrui Zhao, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9149925/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background With advances in systemic therapy, survival has improved in patients with breast cancer brain metastases (BCBM). Radiotherapy (RT), as a local treatment, further contributes to this improvement. This study investigates the prognostic factors for survival in BCBM patients with a Karnofsky Performance Status (KPS) score ≥ 70 who underwent craniocerebral radiotherapy (CRT). Methods A total of 505 patients with BCBM diagnosed in our hospital from January 2017 to December 2023 were retrospectively explored. Subsequently, Kaplan-Meier method (K-M method) was used to analyze overall survival (OS) and progression-free survival (PFS). Additionally, Clinical data were collected, radiomics and dosimetric factors were extracted for univariate and multivariate model analysis, and a survival prediction model was established. Results The median overall survival (mOS) of the 505 BCBM patients was 20.8 months (95% CI 18.8–23.2 months). Multivariate analysis identified the number (≤ 4) of brain metastases (P < 0.001) and CRT (P < 0.001) as independent prognostic factors. Specifically, the median OS in the CRT group (n = 293) was 27.0 months (95% CI 23.33–30.50 months), which was significantly longer than that of the non-radiotherapy group (n = 212), which had a median OS of 15.10 months (95% CI 10.97–17.17 months). A significant survival difference was observed between the two groups (P < 0.001, HR 0.522, 95% CI 0.424–0.632). Furthermore, Multivariate analysis revealed that leptomeningeal metastasis (LM) (P = 0.015), extracranial metastasis (P = 0.015), and intracranial progression after RT (P = 0.013) were independent adverse prognostic factors for OS in patients receiving CRT. Additionally, the median progression-free survival (PFS) in the radiotherapy group was 16.3 months (95% CI 14.6–19.17 months), with LM (P < 0.001) identified as an independent adverse prognostic factor for PFS. In the subgroup analysis, patients with positive expression of human epidermal growth factor receptor 2 (HER2) had a better survival benefit when treated with targeted therapy (TT) (P = 0.021). Finally, a predictive model incorporating radiomic and radiodosimetric features (n = 149) was developed and showed excellent performance in predicting 1-, 2-, and 3-year survival, with area under curve (AUC) values of 0.965, 0.861, and 0.859, respectively. Conclusion For BCBM patients with a KPS ≥ 70, CRT is associated with a significant survival benefit. However, the development of LM remains a major adverse factor leading to poorer overall prognosis. Besides, the integration of radiomic and radiodosimetric features into predictive models demonstrates strong potential for accurately estimating prognosis. These findings suggest that such models could enhance clinical decision-making, ultimately supporting improved patient outcomes. Breast cancer brain metastases Craniocerebral radiotherapy Survival outcomes Predictive modeling Radiomics and radiodosomics Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Breast cancer (BC) has the second highest incidence of brain metastasis (BM) after lung cancer, and is one of the leading causes of death in affected patients ( 1 ). Previous studies have shown that among patients with stage IV breast cancer, those who develop BM exhibit the poorest site-specific survival and overall survival across all distant metastatic sites ( 2 ). Therefore, identifying and intervening in prognostic factors associated with survival has become particularly critical for patients with BCBM. Currently, systemic therapy has improved the survival of patients with BCBM. The primary cause of death in most of these patients remains extracranial disease progression leading to organ failure ( 3 – 5 ). Intracranial disease control is achieved mainly through RT ( 6 ). However, some studies have indicated that the benefits of CRT may not translate into long-term survival improvement ( 7 ). One contributing factor is that a lower KPS score in irradiated patients serves as an independent prognostic factor for both intracranial PFS and OS ( 8 ). A prospective clinical study enrolling patients with a KPS score > 70 who underwent stereotactic radiosurgery (SRS) demonstrated significant OS benefits ( 9 ). This is primarily because patients in poor general condition face an increased risk of radiotherapy-related toxicities, which may lead to treatment intolerance and potential risk-benefit imbalance, ultimately exacerbating intracranial reactions and clinical symptoms ( 10 ). Consequently, both American Society of Clinical Oncology (ASCO) and American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend SRS or whole-brain radiotherapy (WBRT) for BM patients with a KPS score > 70 to achieve improved survival outcomes ( 11 – 13 ). With advancements in imaging technology, a growing number of patients are diagnosed and treated at an early stage when their KPS score remains relatively high ( 14 ). In this study, we primarily enrolled BCBM patients with a KPS score ≥ 70 for analysis. The aim was to compare whether RT could prolong survival in this generally well-performing patient population. Subsequently, univariate and multivariate analyses were performed to identify prognostic factors associated with PFS and OS among those undergoing RT. Furthermore, a cohort of 149 patients with complete RT planning images and dose distribution data was included to develop a predictive model for survival outcomes. The model's performance was evaluated at the 1-, 2-, and 3-year time points using multiple metrics, and a nomogram was created for visual interpretation of the results. Materials and Methods: Data Collection Female patients with BCBM, confirmed radiologically or histologically at our hospital between January 2017 and December 2023, were retrospectively enrolled. The inclusion criteria were as follows: 1. Histologically or cytologically confirmed BC; 2. BM confirmed by cranial Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or pathological report; 3. Age ≥ 18 years with complete clinical data. The patient screening process is illustrated in Fig. 1 . Furthermore, treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. Regarding survival endpoints: Median overall survival (mOS) was defined as the time from the diagnosis of brain metastasis to death from any cause or the last follow-up. Radiation-specific overall survival (RT-OS) was defined as the time from the initiation of cranial radiotherapy to death from any cause or the last follow-up. Radiation-specific progression-free survival (RT-PFS) was defined as the time from the initiation of cranial radiotherapy to intracranial disease progression or death from any cause. Patient Follow-up Follow-up information was collected through medical record review and telephone interviews. The unified follow-up cutoff date was set as December 10, 2024. The former approach involved retrieving data from outpatient visits and hospital admissions. Additionally, all patients underwent a standardized telephone interview at the time of their last follow-up. Statistical Analysis Collected data were organized and categorized, and statistical analysis and visualization were performed using SPSS 26.0 and R 4.3.0 software. Variables in the baseline characteristics were treated as qualitative data, and differences between groups were assessed using the chi-square test (χ² test). In cases where significant imbalances in baseline characteristics were observed between the radiotherapy and non-radiotherapy groups, Inverse Probability of Treatment Weighting was applied to adjust for confounding factors before further survival analysis. The main analytical procedures included: 1. K-M method to plot survival curves for the overall population and subgroup populations; 2. Log-rank test to evaluate survival differences between groups; 3. Univariate and multivariate Cox proportional hazards regression models to identify factors associated with survival. Variables with a P < 0.1 in univariate analysis were included in the multivariate analysis (backward stepwise method; statistical significance set at P < 0.05) to determine independent prognostic factors. 4. Additionally, subgroup analyses based on estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) receptor status and treatment modalities were conducted using Cox regression models, and forest plots were generated to visualize the results. Predictive Modeling DICOM CT images and dose distribution maps acquired prior to treatment from 149 patients undergoing cranial radiotherapy were utilized for feature extraction. This process was performed using 3D Slicer software (version 5.6.2). A total of 851 original features were extracted from the CT images and dose maps collectively. Subsequently, feature selection was conducted using Least Absolute Shrinkage and Selection Operator (LASSO) regression combined with multivariate Cox regression analysis. Features with a significance level of P < 0.05 were incorporated into the predictive model. To evaluate model performance, multiple metrics were applied, including the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and clinical decision curve analysis (DCA). These evaluations were performed at the 1‑, 2‑, and 3‑year survival timepoints. Finally, a nomogram was developed to visually represent the predictive model. Results Baseline characteristics. A total of 505 BCBM patients were included in this study, and their baseline characteristics are summarized in Table 1 . Among them, 293 patients (58.02%) received CRT, while 212 patients (41.98%) did not. The median age was 47 years, and 42.77% of patients were younger than 45 years, suggesting a trend toward younger age at BM diagnosis. Additionally, a relatively high proportion of patients presented with locally advanced disease, and 23.96% had distant metastases at initial diagnosis, with 8.7% having BM at first presentation. According to molecular subtyping based on pathological results, 51.29% of patients were ER+, 36.44% were HER2+, and 14.46% had triple-negative breast cancer (TNBC). In terms of metastatic features, 80.2% of patients had a maximum lesion diameter smaller than 1 cm, and the majority had fewer than 4 metastatic lesions. Regarding treatment, only 8.32% of patients underwent surgical resection of BM, while the majority (62.97%) received chemotherapy. Based on ER and HER2 expression status, some patients also received endocrine therapy (ET) (22.77%) and/or targeted therapy (TT) (24.95%). Table 1 Baseline Characteristics of 505 Breast Cancer Brain Metastasis Patients: Comparison Between Radiotherapy and Non-Radiotherapy Groups. HER2: Human Epidermal Growth Factor Receptor 2. Histological grade, n (%) Total (n = 505) No brain radiotherapy (n = 212) Brain radiotherapy (n = 293) unknown 304 (60.2) 131 (61.79) 173 (59.04) I grade 6 (1.19) 3 (1.42) 3 (1.02) II grade 112 (22.18) 45 (21.23) 67 (22.87) III grade 83 (16.44) 33 (15.57) 50 (17.06) Estrogen receptor, n (%) Negative 194 (38.42) 71 (33.49) 123 (41.98) Positive 259 (51.29) 106 (50.00) 153 (52.22) unknown 52 (10.3) 35 (16.51) 17 (5.80) age,n (%) <45 216 (42.77) 86 (40.57) 130 (44.37) ≥ 45 289 (57.23) 126 (59.43) 163 (55.63) Menopausal conditions, n (%) No 314 (62.18) 119 (56.13) 195 (66.55) Yes 191 (37.82) 93 (43.87) 98 (33.45) T stage, n (%) T1 43 (8.51) 15 (7.08) 28 (9.56) T2 150 (29.7) 52 (24.53) 98 (33.45) T3 58 (11.49) 27 (12.74) 31 (10.58) T4 110 (21.78) 44 (20.75) 66 (22.53) Tx 144 (28.51) 74 (34.91) 70 (23.89) N stage, n (%) N0 75 (14.85) 31 (14.62) 44 (15.02) N1 126 (24.95) 46 (21.70) 80 (27.30) N2 88 (17.43) 29 (13.68) 59 (20.14) N3 102 (20.2) 42 (19.81) 60 (20.48) Nx 114 (22.57) 64 (30.19) 50 (17.06) M stage, n (%) M0 384 (76.04) 148 (69.81) 236 (80.55) M1 121 (23.96) 64 (30.19) 57 (19.45) Pathological pattern, n (%) Non-invasive carcinoma 19 (3.76) 10 (4.72) 9 (3.07) Invasive carcinoma 453 (89.7) 180 (84.91) 273 (93.17) unknown 33 (6.53) 22 (10.38) 11 (3.75) Neoadjuvant chemotherapy, n (%) No 278 (55.05) 134 (63.21) 144 (49.15) Yes 227 (44.95) 78 (36.79) 149 (50.85) HER2, n (%) Negative 183 (36.24) 70 (33.02) 113 (38.57) Positive 184 (36.44) 56 (26.42) 128 (43.69) unknown 138 (27.33) 86 (40.57) 52 (17.75) Molecular subtyping, n (%) Luminal A 44 (8.71) 13 (6.13) 31 (10.58) Luminal B 188 (37.23) 81 (38.21) 107 (36.52) HER2 overexpression type 94 (18.61) 27 (12.74) 67 (22.87) Triple negative type 73 (14.46) 31 (14.62) 42 (14.33) unknown 106 (20.99) 60 (28.30) 46 (15.70) Breast Surgery, n (%) No 114 (22.57) 60 (28.30) 54 (18.43) Radical surgery 332 (65.74) 122 (57.55) 210 (71.67) Breast-conserving surgery 31 (6.14) 14 (6.60) 17 (5.80) unknown 28 (5.54) 16 (7.55) 12 (4.10) Adjuvant chemotherapy, n (%) No 194 (38.42) 83 (39.15) 111 (37.88) Yes 311 (61.58) 129 (60.85) 182 (62.12) Radiotherapy for the Breast, n (%) No 284 (56.24) 127 (59.91) 157 (53.58) Yes 221 (43.76) 85 (40.09) 136 (46.42) Maintenance treatment, n (%) No 240 (47.52) 108 (50.94) 132 (45.05) Endocrine Therapy 119 (23.56) 49 (23.11) 70 (23.89) Targeted Therapy 50 (9.9) 13 (6.13) 37 (12.63) Endocrine and targeted therapy 32 (6.34) 11 (5.19) 21 (7.17) Chemotherapy 64 (12.67) 31 (14.62) 33 (11.26) Size of brain metastases, n (%) ≤ 1cm 405 (80.2) 172 (81.13) 233 (79.52) >1cm 100 (19.8) 40 (18.87) 60 (20.48) Number of brain metastases, n (%) ≤ 4 344 (68.12) 160 (75.47) 184 (62.80) >4 161 (31.88) 52 (24.53) 109 (37.20) Leptomeningeal metastases, n (%) No 455 (90.1) 182 (85.85) 273 (93.17) Yes 50 (9.9) 30 (14.15) 20 (6.83) Location of brain metastases, n (%) Supratentorial transfer 247 (48.91) 116 (54.72) 131 (44.71) Subtentorial transfer 240 (47.52) 96 (45.28) 144 (49.15) unknown 18 (3.56) 0 (0.00) 18 (6.14) Clinical symptoms, n (%) No 287 (56.83) 139 (65.57) 148 (50.51) Yes 218 (43.17) 73 (34.43) 145 (49.49) Craniocerebral surgery, n (%) No 463 (91.68) 192 (90.57) 271 (92.49) Yes 42 (8.32) 20 (9.43) 22 (7.51) Endocrine Therapy, n (%) No 390 (77.23) 173 (81.60) 217 (74.06) Yes 115 (22.77) 39 (18.40) 76 (25.94) Chemotherapy, n (%) No 187 (37.03) 96 (45.28) 91 (31.06) Yes 318 (62.97) 116 (54.72) 202 (68.94) Targeted Therapy, n (%) No 379 (75.05) 176 (83.02) 203 (69.28) Yes 126 (24.95) 36 (16.98) 90 (30.72) Analysis of survival prognosis. The median follow-up time for the entire cohort was 40.5 months (95% CI: 37.27–46.27 months). As shown in the K-M curve in Fig. 2 A, the OS for the total population was 20.8 months (95% CI: 18.8–23.2 months). Univariate and multivariate analyses (Supplementary Table 1) indicated that the number of BM, LM, infratentorial metastasis, cranial surgery, CRT, and chemotherapy were associated with OS in BCBM patients. Notably, fewer than 4 brain metastases (P < 0.001) and CRT (P < 0.001) were identified as independent prognostic factors. Therefore, K-M survival analysis was performed comparing the radiotherapy and non-radiotherapy groups (Fig. 2 B). The mOS was 27.0 months (95% CI: 23.33–30.50 months) in the radiotherapy group (n = 293) and 15.10 months (95% CI: 10.97–17.17 months) in the non-radiotherapy group (n = 212), demonstrating a statistically significant difference between the two groups (P < 0.001; HR: 0.522; 95% CI: 0.424–0.632). These results suggest that radiotherapy significantly improves OS in BCBM with a KPS score ≥ 70, with particularly pronounced short-term survival benefits. Further analysis of survival outcomes in the CRT cohort revealed that, as shown in the K-M curve in Fig. 2 C, the RT-OS, defined as the time from RT initiation to death or last follow-up, was 22.9 months (95% CI: 20.5–27.0 months). According to univariate and multivariate analyses (Table 2 ), factors associated with reduced survival included Ki67 > 14%, LM, WBRT, ECM, and intracranial progression after RT. The LM (P = 0.015), ECM (P = 0.015), and intracranial progression after RT (P = 0.013) were identified as independent adverse prognostic factors for OS in irradiated patients. Additionally, the RT-PFS was 16.3 months (95% CI: 14.6–19.17 months; Fig. 2 D). Notably, LM (P < 0.001) was an independent adverse prognostic factor for PFS in this population (Supplementary Table 2). In the overall cohort, patients with LM had a mOS of 13.43 months (95% CI: 10.37–19.17 months), while irradiated patients with this condition exhibited a median RT-OS of 12.37 months (95% CI: 7.37–NA months). These results indicate that RT may not significantly improve survival in patients with LM, however, this conclusion should be interpreted with caution due to the limited sample size, which may introduce bias. Furthermore, patients with stable intracranial disease after RT achieved longer survival, whereas those with ECM experienced poorer overall outcomes. Table 2 Univariate and Multivariate Analysis of Survival in 293 BCBM Patients Treated with RT. HER2: Human Epidermal Growth Factor Receptor 2; SRS: Stereotactic Radiosurgery; WBRT: Whole Brain Radiation Therapy. Variables Univariate analysis Multivariate analysis P HR (95%CI) P HR (95%CI) Age >45 1.00 (Reference) ≤45 0.832 0.97 (0.73 ~ 1.29) Pathological pattern Invasive carcinoma 1.00 (Reference) Other 0.491 0.79 (0.40 ~ 1.55) Estrogen receptor Unknow 1.00 (Reference) Positive 0.444 1.31 (0.66 ~ 2.59) Negative 0.335 1.40 (0.70 ~ 2.80) HER2 Unknow 1.00 (Reference) Positive 0.822 1.05 (0.69 ~ 1.60) Negative 0.222 1.30 (0.85 ~ 1.97) Ki67 1cm 1.00 (Reference) ≤1cm 0.587 1.11 (0.76 ~ 1.62) Unknow 0.118 1.73 (0.87 ~ 3.42) Number of brain metastases >4 1.00 (Reference) 1.00 (Reference) ≤4 0.179 0.78 (0.55 ~ 1.12) 0.480 0.88 (0.60 ~ 1.27) Unknow 0.032 1.59 (1.04 ~ 2.42) 0.084 1.47 (0.95 ~ 2.29) Leptomeningeal metastases No 1.00 (Reference) 1.00 (Reference) Yes 0.015 2.03 (1.15 ~ 3.59) 0.015 2.09 (1.15 ~ 3.77) Location of brain metastases Unknow 1.00 (Reference) Supratentorial transfer 0.492 0.81 (0.44 ~ 1.49) Subtentorial transfer 0.703 1.12 (0.62 ~ 2.05) Clinical symptoms No 1.00 (Reference) Yes 0.899 0.98 (0.74 ~ 1.31) Craniocerebral surgery No 1.00 (Reference) 1.00 (Reference) Yes 0.069 0.58 (0.32 ~ 1.04) 0.532 0.82 (0.43 ~ 1.55) Endocrine Therapy No 1.00 (Reference) Yes 0.440 0.88 (0.63 ~ 1.22) Chemotherapy No 1.00 (Reference) Yes 0.906 0.98 (0.71 ~ 1.35) Targeted Therapy No 1.00 (Reference) Yes 0.779 0.95 (0.66 ~ 1.36) Methods of radiotherapy SRS 1.00 (Reference) 1.00 (Reference) WBRT < .001 0.56 (0.41 ~ 0.77) 0.119 0.75 (0.52 ~ 1.08) Concomitant medications for radiotherapy No 1.00 (Reference) Yes 0.727 0.95 (0.70 ~ 1.28) Extracranial metastasis No 1.00 (Reference) 1.00 (Reference) Yes 0.002 1.83 (1.25 ~ 2.69) 0.015 1.68 (1.10 ~ 2.54) Intracranial progression after radiotherapy No 1.00 (Reference) 1.00 (Reference) Yes < .001 0.60 (0.44 ~ 0.81) 0.013 0.67 (0.48 ~ 0.92) Subgroup Analysis. As shown in the forest plot in Supplementary Fig. 1A, ET did not significantly improve survival outcomes in ER+ patients after RT. This may be attributed to the fact that the benefits of ET are typically observed in long-term survival, whereas this patient population had relatively shorter OS, thereby limiting observable benefits. Overall, trends suggested that chemotherapy, TT, cranial surgery, or SRS were associated with better survival in these patients, although these differences were not statistically significant. In Supplementary Fig. 1B, HER2 + patients receiving TT showed improved survival outcomes. This included not only HER2-directed targeted agents but also a small subset of patients who received anti-angiogenic targeted therapy. The results indicate that both types of TT contributed to prolonged survival in BM patients to some extent. Development of the Predictive Model. The predictive model was developed by integrating radiomic and dosimetric features with clinical factors from 149 patients. As illustrated in Supplementary Fig. 2, all extracted features underwent min-max normalization. Through cross-validation, the parameter λ was adjusted to identify survival-associated features. Feature selection was performed using LASSO regression combined with multivariate Cox analysis, incorporating features with P < 0.05. The optimal λ value (Lambda.1se) was determined to be 0.04882492, resulting in the selection of 9 feature factors in Fig. 3 . The coefficients of the feature factors were as follows: 0.201239759、-0.094642364、0.072927215、-0.035393399、-0.228740902、0.189803755、0.089741358、-0.312898484、0.170645305。Ultimately, the aforementioned nine features were incorporated to construct predictive models for 1-year, 2-year, and 3-year survival. The survival nomogram visually predicts the 1-, 2-, and 3-year OS rates for BCBM patients (Fig. 3 ). In terms of performance across the constructed time-dependent predictive models, the 1-year survival model demonstrated the highest predictive accuracy. As shown in Fig. 4ABC, time-dependent receiver operating characteristic (ROC) curve analysis revealed AUC values of 0.965, 0.861, and 0.859 for 1-, 2-, and 3-year survival predictions, respectively. Specifically, the 1-year survival prediction showed a sensitivity of 1.000, specificity of 0.829, and accuracy of 0.832; the 2-year prediction had a sensitivity of 1.000, specificity of 0.681, and accuracy of 0.711; and the 3-year prediction achieved a sensitivity of 0.973, specificity of 0.455, and accuracy of 0.584. Furthermore, the calibration curves for 1-, 2-, and 3-year survival predictions (Fig. 4DEF) indicated minimal deviation between predicted and observed outcomes, suggesting good model reliability. In conclusion, the integration of clinical factors, radiotherapy radiomics, and radiodosimetric features holds significant clinical utility for predicting 1-, 2-, and 3-year survival in BCBM patients. This approach provides valuable guidance for improving outcomes in this population; however, the predictive performance gradually decreases as the survival time frame extends. Discussion This study, based on single-center data, analyzed the prognosis of BCBM patients. The results indicate that CRT is associated with a significant survival benefit in BCBM patients with a KPS score ≥ 70. The overall survival observed in our cohort is consistent with current published findings ( 15 , 16 ). After the development of BM, survival in BM patients is primarily influenced by the characteristics of the BM and the treatment strategies employed ( 17 , 18 ). RT, as one of the main treatment modalities for BM, improves local control rates ( 19 , 20 ). Importantly, our study demonstrates that RT not only enhances local control but also significantly improves OS in irradiated patients. Furthermore, patients who achieved stable intracranial disease after RT showed pronounced benefits in long-term survival. Systemic therapy also plays a crucial role in the long-term survival of BCBM patients. Currently, the majority of patients receive chemotherapy for disease control, while only a minority undergo ET or TT ( 21 ). For HER2 + patients, existing studies have demonstrated that TT can prolong survival in those with BM ( 15 ). A real-world multicenter study ( 22 ) indicated that patients receiving CRT combined with pyrotinib achieved improved survival outcomes. Additionally, a phase 3 trial showed ( 23 ) that pyrotinib plus capecitabine significantly improved PFS compared to lapatinib plus capecitabine, providing an alternative treatment option for HER2 + metastatic BC patients after trastuzumab and chemotherapy. In the present study, although the use of TT after BM did not demonstrate a statistically significant improvement in OS or PFS among irradiated patients overall, subgroup analysis revealed a survival benefit in HER2 + patients who received TT alongside CRT. Based on these findings, HER2 + BCBM patients with good performance status are likely to achieve prolonged survival through a combination of CRT and TT. In this study, only 50 (9.9%) BC patients were diagnosed with LM via MRI. Among these LM patients, 30 (60%) received RT; however, they still exhibited poor survival outcomes despite this intervention. Previous studies have similarly reported significantly worse prognosis in patients with LM ( 24 , 25 ). On one hand, current imaging techniques require further improvement to enable earlier detection of LM ( 26 ). On the other hand, effective treatment strategies for LM remain limited. The main approach involves a combination of systemic therapy and local treatment; however, the efficacy of systemic agents is often constrained by the BBB ( 27 , 28 ). Although recent studies suggest that small-molecule targeted therapies may improve survival in HER2 + BC patients with LM ( 29 ), no clinical trials have yet explored whether combining RT with TT provides additional benefits for this specific population. Further investigation is needed to address this question. Predictive models utilize existing data to estimate an individual's risk of developing a disease or experiencing a specific future outcome, and they already offer valuable guidance in clinical practice. For instance, a study by Josef A. Buchner et al. ( 30 ) employed radiomics to predict local control in BM patients following postoperative stereotactic radiotherapy. Similarly, another study based on a prospective trial predicted treatment response and overall survival in breast cancer brain metastasis patients treated with stereotactic radiosurgery ( 31 ). While these models demonstrated good predictive value, they incorporated a relatively limited set of variables. Currently, many studies integrate clinical and radiomic features to predict local control after RT for BM, and the combination of these factors has been shown to significantly enhance model performance ( 32 , 33 ). The present study is the first to incorporate clinical variables, radiotherapy imaging features, and radiodosimetric parameters into a unified predictive model for survival prognosis in BCBM patients. The model validation results indicate strong predictive accuracy, suggesting its potential utility in guiding clinical management and improving survival outcomes for this patient population. This study has several inherent limitations. First, as a single-center retrospective analysis, the results are subject to potential selection bias, which may affect the accuracy and generalizability of the findings. Second, the study spans a relatively long period, during which changes in systemic treatment strategies and advancements in radiotherapy techniques may have influenced patient outcomes. These temporal variations could introduce confounding effects that impact the interpretation of the data and the validity of the conclusions. Finally, the sample size used to develop the predictive model was relatively small. Therefore, the conclusions require validation in larger, multicenter prospective cohort studies, as well as further verification using external datasets or prospective data. Conclusion In summary, BCBM patients with good performance status can achieve long-term survival benefits from CRT, particularly when local control of intracranial lesions is maintained, which is associated with significantly prolonged OS. However, the development of LM leads to a substantially worse overall prognosis. Therefore, early detection and timely intervention for LM are critically important. Our predictive model demonstrates strong performance in estimating patient prognosis. In the future, incorporating additional relevant factors could further enhance its accuracy, ultimately enabling more effective prediction of outcomes in BCBM patients, guiding clinical decision-making, and thereby contributing to improved survival and patient support. Abbreviations Full title radiotherapy RT breast cancer patients with brain metastases BCBM Karnofsky Performance Status KPS craniocerebral radiotherapy CRT Kaplan-Meier K-M median overall survival mOS leptomeningeal metastasis LM extracranial metastasis ECM area under curve AUC Breast cancer BC brain metastasis BM stereotactic radiosurgery SRS American Society of Clinical Oncology ASCO American Society for Therapeutic Radiology and Oncology ASTRO whole-brain radiotherapy WBRT Computed Tomography CT Magnetic Resonance Imaging MRI Radiation-specific overall survival RT-OS Radiation-specific progression-free survival RT-PFS Least Absolute Shrinkage and Selection Operator LASSO receiver operating characteristic ROC clinical decision curve analysis DCA triple-negative breast cancer TNBC endocrine therapy ET targeted therapy TT Human Epidermal Growth Factor Receptor 2 HER2 estrogen receptor ER Declarations Conflict of interest The authors declare that they have no conflicts of interest. Ethics approval and consent to participate This study was approved by the Ethics Committee of Yunnan Cancer Hospital (approval number: SLKYLX2025-219), and the experimental procedures were conducted in accordance with the relevant regulations and in strict compliance with the Declaration of Helsinki. Informed consent to participate was obtained from all participants also. Consent for publication Written informed consent for publication was obtained from all participants. CRediT authorship contribution statement Man Li (First Author): Conceptualization, Validation, Formal analysis, Investigation, Data Curation, Writing-Original Draft. Yuchen, Ge: Formal analysis, Investigation, Writing-Review & Editing. Tao Wei: Software, Data Curation, Methodology. Yifan Lei: Software, Data Curation. Yunyan Yang: Investigation, Data Curation. Mingrui Zhao: Data Curation, Visualization. Bo Li: Data Curation, Methodology. Wenhui Li (Corresponding author): Resources, Project administration, Conceptualisation, Writing - Review & Editing, Funding acquisition. Li Wang (Corresponding author): Resources, Conceptualisation, Project administration, Writing - Review & Editing, Funding acquisition. Funding Information and Acknowledgements This work was financially supported by the National Natural Science Foundation of China (82460576), Xingdian Talents Support Program for young Talents (XDYC-QNRC-2023-0189) and Yunnan Provincial Health Commission Medical Reserve Talent Training Program(H2024022). Data availability The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Clinical trial number Not applicable. References Giaquinto AN, Sung H, Newman LA, Freedman RA, Smith RA, Star J, et al. Breast cancer statistics 2024. Cancer J Clin. 2024;74(6):477–95. Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. 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Estermann A, Schneider C, Zimmermann F, Papachristofilou A, Finazzi T. Whole brain radiation therapy for patients with brain metastases: survival outcomes and prognostic factors in a contemporary institutional series. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al]. 2024;200(11):942–8. Freeman M, Ennis M, Jerzak KJ. Karnofsky Performance Status (KPS) ≤ 60 Is Strongly Associated With Shorter Brain-Specific Progression-Free Survival Among Patients With Metastatic Breast Cancer With Brain Metastases. Front Oncol. 2022;12:867462. Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95. Natesan D, Carpenter DJ, Giles W, Oyekunle T, Niedzwiecki D, Reitman ZJ, et al. Clinical Factors Associated With 30-Day Mortality Among Patients Undergoing Radiation Therapy for Brain Metastases. Adv radiation Oncol. 2023;8(4):101211. Vogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S, Cahill D, et al. Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(5):492–516. Schiff D, Messersmith H, Brastianos PK, Brown PD, Burri S, Dunn IF, et al. Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(20):2271–6. Gondi V, Bauman G, Bradfield L, Burri SH, Cabrera AR, Cunningham DA, et al. Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. Practical radiation Oncol. 2022;12(4):265–82. Rosen J, Werner JM, Ceccon GS, Rosen EK, Wollring MM, Stetter I, et al. MRI and (18)F-FET PET for Multimodal Treatment Monitoring in Patients with Brain Metastases: A Cost-Effectiveness Analysis. Journal of nuclear medicine: official publication. Soc Nuclear Med. 2024;65(6):838–44. Yan M, Ouyang Q, Sun T, Niu L, Yang J, Li L, et al. Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial. EClinicalMedicine. 2024;76:102837. Li X, Sun Y, Tang L, Li Y, Yang X. Treatment of metastatic breast cancer by stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS). Discover Oncol. 2024;15(1):733. Grinda T, Aizer AA, Lin NU, Sammons SL. Central Nervous System Metastases in Breast Cancer. Curr Treat Options Oncol. 2025;26(1):14–35. Bécourt S, Cheymol C, Cren PY, Mouttet-Audouard R. [Brain metastases in breast cancer: Diagnosis and management]. Bulletin du cancer; 2025. van Schie P, Huisman RG, Wiersma T, Knegjens JL, Navran A, Brandsma D, et al. Local control and toxicity after stereotactic radiotherapy in brain metastases patients and the impact of novel systemic treatments. Radiotherapy oncology: J Eur Soc Therapeutic Radiol Oncol. 2024;200:110540. Fabian A, Buergy D, Weykamp F, Hörner-Rieber J, Bernhardt D, Boda-Heggemann J, et al. Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study. Clin Exp Metastasis. 2024;42(1):6. Garrone O, Ruatta F, Rea CG, Denaro N, Ghidini M, Cauchi C et al. Current Evidence in the Systemic Treatment of Brain Metastases from Breast Cancer and Future Perspectives on New Drugs, Combinations and Administration Routes: A Narrative Review. Cancers. 2024;16(24). Huang J, Sun S, Tan Q, Zheng F, Zhou D, Man X, et al. Effectiveness and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-Positive Breast Cancer Patients with Brain Metastases: A Multicenter Real-World Study. Clin Breast Cancer. 2024;24(6):e509. -e18.e1 . Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(3):351–60. Morikawa A, Jordan L, Rozner R, Patil S, Boire A, Pentsova E, et al. Characteristics and Outcomes of Patients With Breast Cancer With Leptomeningeal Metastasis. Clin Breast Cancer. 2017;17(1):23–8. Huppert LA, Fisch S, Tsopurashvili E, Somepalle SS, Salans M, Vasudevan HN, et al. Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study. Breast Cancer Res Treat. 2024;206(3):625–36. Cohen-Nowak AJ, Hill VB, Kumthekar P. Diagnostics and Screening in Breast Cancer with Brain and Leptomeningeal Metastasis: A Review of the Literature. Cancers. 2024;16:21. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–41. Bartsch R, Jerzak KJ, Larrouquere L, Müller V, Le Rhun E. Pharmacotherapy for leptomeningeal disease in breast cancer. Cancer Treat Rev. 2024;122:102653. Id Said B, Jerzak KJ, Chen H, Moravan V, Warner E, Myrehaug S, et al. Survival outcomes among patients with breast cancer and leptomeningeal disease. Sci Rep. 2025;15(1):24170. Buchner JA, Kofler F, Mayinger M, Christ SM, Brunner TB, Wittig A, et al. Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy. Neurooncology. 2024;26(9):1638–50. Katsos K, Michalopoulos G, D'Ambrosio AL, Cobb WS, Grills IS, McInerney J et al. Predictors of treatment response and overall survival in patients with breast cancer brain metastases treated with stereotactic radiosurgery: a prospective study using the NeuroPoint Alliance SRS Registry. J Neurosurg. 2025:1–12. Kanakarajan H, De Baene W, Hanssens P, Sitskoorn M. Predicting local control of brain metastases after stereotactic radiotherapy with clinical, radiomics and deep learning features. Radiation Oncol (London England). 2024;19(1):182. Volovăț CC, Buzea CG, Boboc DI, Ostafe MR, Agop M, Ochiuz L et al. Hybrid Deep Learning for Survival Prediction in Brain Metastases Using Multimodal MRI and Clinical Data. Diagnostics (Basel Switzerland). 2025;15(10). Additional Declarations No competing interests reported. Supplementary Files Supplement.docx Supplement.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 08 May, 2026 Reviewers invited by journal 06 May, 2026 Editor assigned by journal 19 Mar, 2026 Submission checks completed at journal 19 Mar, 2026 First submitted to journal 17 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9149925","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":637381720,"identity":"fc2d2aa9-5f72-45c7-b41e-40a57880e3b3","order_by":0,"name":"Man Li","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Man","middleName":"","lastName":"Li","suffix":""},{"id":637381721,"identity":"52b30703-c29e-4aef-b966-c0b1a92e3a5d","order_by":1,"name":"yuchen Ge","email":"","orcid":"","institution":"Kunming University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"yuchen","middleName":"","lastName":"Ge","suffix":""},{"id":637381722,"identity":"77af5075-a446-4d6f-8a78-c0fe5fac20f6","order_by":2,"name":"tao Wei","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"tao","middleName":"","lastName":"Wei","suffix":""},{"id":637381723,"identity":"89de7eb9-4896-4511-a721-a1072d1b7c1c","order_by":3,"name":"yifan Lei","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"yifan","middleName":"","lastName":"Lei","suffix":""},{"id":637381724,"identity":"31ea6aa6-a69a-43ae-8dc5-3beb28105596","order_by":4,"name":"yunyan Yang","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"yunyan","middleName":"","lastName":"Yang","suffix":""},{"id":637381725,"identity":"6ee471c5-369f-4bbe-8b3c-da43dba414e2","order_by":5,"name":"mingrui Zhao","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"mingrui","middleName":"","lastName":"Zhao","suffix":""},{"id":637381726,"identity":"0515b931-6126-4adb-88a4-01700f72f8cc","order_by":6,"name":"bo Li","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"bo","middleName":"","lastName":"Li","suffix":""},{"id":637381727,"identity":"aefd3112-81fd-444e-aab8-e958963cae10","order_by":7,"name":"wenhui Li","email":"","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"wenhui","middleName":"","lastName":"Li","suffix":""},{"id":637381728,"identity":"4342170f-e370-4cc2-a3dc-9801b4b33aff","order_by":8,"name":"li Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYLCCBwY2BhAWG7FaEgzSSNbCcJgELQbHzx5+kVBw3lh32hkDhg9lhxn4ZzcQ0HImL80iweC2mdntHAPGGecOM0jcOYBfi9mBHDMDoBYbkBZm3rbDDAYSCQS0nH8D0nIOouUvUVpu5Bg/SDA4AHYYMyMxWuxvvDEDBnKysdnttIKDPefSeSRuENAi2Z9j/OHDHzvDbbeTNz74UWYtxz+DgBYgYJOAsQ4AMQ9B9UDA/IEYVaNgFIyCUTCCAQAifkTWTaxcjgAAAABJRU5ErkJggg==","orcid":"","institution":"Yunnan Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"li","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-03-17 14:24:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9149925/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9149925/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109297788,"identity":"51d3d3b7-b5d3-4093-b107-cb2abb69d1c7","added_by":"auto","created_at":"2026-05-15 09:05:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53669,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient screening and enrollment. KPS: Karnofsky performance status. CT: Computed tomography.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/415e943a0b5fe9a9341718f6.png"},{"id":109286645,"identity":"92e4900c-6397-4268-8f71-16f82fff73e2","added_by":"auto","created_at":"2026-05-15 02:36:02","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78093,"visible":true,"origin":"","legend":"\u003cp\u003eOS and PFS of BCBM Patients Analyzed by Kaplan-Meier Method with Log-Rank Test. (A) OS of the entire cohort from the time of BM diagnosis. (B) Comparison of OS between patients who received CRT and those who did not. (C) RT-OS from the initiation of CRT in the treated subgroup. (D) RT-PFS from the initiation of CRT in the treated subgroup. RT: Radiation therapy.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/3c74ad7bf75b17eb41286999.jpeg"},{"id":109297829,"identity":"b375df65-2832-425a-8717-52cef9d5b375","added_by":"auto","created_at":"2026-05-15 09:06:31","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":251601,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram for Predicting 1-, 2-, and 3-Year Survival Based on Clinical Factors, Radiomic Features, and Dosimetric Features.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/052e21fee0d3186b57b013af.jpeg"},{"id":109286649,"identity":"6eb8cbc0-772a-432a-988a-9785dc2a8fba","added_by":"auto","created_at":"2026-05-15 02:36:02","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":74632,"visible":true,"origin":"","legend":"\u003cp\u003ePerformance Evaluation of the Survival Prediction Model. (A) ROC curve for 1-year survival prediction. (B) ROC curve for 2-year survival prediction. (C) ROC curve for 3-year survival prediction. (D) Calibration curve for 1-year survival prediction. (E) Calibration curve for 2-year survival prediction. (F) Calibration curve for 3-year survival prediction.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/d63655610414220f82f714d7.jpeg"},{"id":109296192,"identity":"9e0d80c7-2af0-40ae-8bae-4f0164e64ebb","added_by":"auto","created_at":"2026-05-15 08:46:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":650895,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/ee87ae04-8ba1-4644-8206-e87f6f270939.pdf"},{"id":109286644,"identity":"93bafe14-0533-428e-8526-97ae479b60b2","added_by":"auto","created_at":"2026-05-15 02:36:02","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":503417,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/d792a4957de5eb0115da1f9b.docx"},{"id":109296641,"identity":"0d82be7c-50dc-43d4-a2d2-96b5c7c52a9b","added_by":"auto","created_at":"2026-05-15 08:48:50","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":503417,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-9149925/v1/6a9996a9f3a86a0ffa5e3730.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Factors Analysis in Breast Cancer Patients with Brain Metastases: Identification of Key Determinants of Survival1","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer (BC) has the second highest incidence of brain metastasis (BM) after lung cancer, and is one of the leading causes of death in affected patients (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Previous studies have shown that among patients with stage IV breast cancer, those who develop BM exhibit the poorest site-specific survival and overall survival across all distant metastatic sites (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Therefore, identifying and intervening in prognostic factors associated with survival has become particularly critical for patients with BCBM.\u003c/p\u003e \u003cp\u003eCurrently, systemic therapy has improved the survival of patients with BCBM. The primary cause of death in most of these patients remains extracranial disease progression leading to organ failure (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Intracranial disease control is achieved mainly through RT (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, some studies have indicated that the benefits of CRT may not translate into long-term survival improvement (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). One contributing factor is that a lower KPS score in irradiated patients serves as an independent prognostic factor for both intracranial PFS and OS (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A prospective clinical study enrolling patients with a KPS score\u0026thinsp;\u0026gt;\u0026thinsp;70 who underwent stereotactic radiosurgery (SRS) demonstrated significant OS benefits (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This is primarily because patients in poor general condition face an increased risk of radiotherapy-related toxicities, which may lead to treatment intolerance and potential risk-benefit imbalance, ultimately exacerbating intracranial reactions and clinical symptoms (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Consequently, both American Society of Clinical Oncology (ASCO) and American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend SRS or whole-brain radiotherapy (WBRT) for BM patients with a KPS score\u0026thinsp;\u0026gt;\u0026thinsp;70 to achieve improved survival outcomes (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). With advancements in imaging technology, a growing number of patients are diagnosed and treated at an early stage when their KPS score remains relatively high (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we primarily enrolled BCBM patients with a KPS score\u0026thinsp;\u0026ge;\u0026thinsp;70 for analysis. The aim was to compare whether RT could prolong survival in this generally well-performing patient population. Subsequently, univariate and multivariate analyses were performed to identify prognostic factors associated with PFS and OS among those undergoing RT. Furthermore, a cohort of 149 patients with complete RT planning images and dose distribution data was included to develop a predictive model for survival outcomes. The model's performance was evaluated at the 1-, 2-, and 3-year time points using multiple metrics, and a nomogram was created for visual interpretation of the results.\u003c/p\u003e"},{"header":"Materials and Methods:","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eFemale patients with BCBM, confirmed radiologically or histologically at our hospital between January 2017 and December 2023, were retrospectively enrolled. The inclusion criteria were as follows: 1. Histologically or cytologically confirmed BC; 2. BM confirmed by cranial Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or pathological report; 3. Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years with complete clinical data. The patient screening process is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. Regarding survival endpoints: Median overall survival (mOS) was defined as the time from the diagnosis of brain metastasis to death from any cause or the last follow-up. Radiation-specific overall survival (RT-OS) was defined as the time from the initiation of cranial radiotherapy to death from any cause or the last follow-up. Radiation-specific progression-free survival (RT-PFS) was defined as the time from the initiation of cranial radiotherapy to intracranial disease progression or death from any cause.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Follow-up\u003c/h3\u003e\n\u003cp\u003eFollow-up information was collected through medical record review and telephone interviews. The unified follow-up cutoff date was set as December 10, 2024. The former approach involved retrieving data from outpatient visits and hospital admissions. Additionally, all patients underwent a standardized telephone interview at the time of their last follow-up.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCollected data were organized and categorized, and statistical analysis and visualization were performed using SPSS 26.0 and R 4.3.0 software. Variables in the baseline characteristics were treated as qualitative data, and differences between groups were assessed using the chi-square test (χ\u0026sup2; test). In cases where significant imbalances in baseline characteristics were observed between the radiotherapy and non-radiotherapy groups, Inverse Probability of Treatment Weighting was applied to adjust for confounding factors before further survival analysis. The main analytical procedures included: 1. K-M method to plot survival curves for the overall population and subgroup populations; 2. Log-rank test to evaluate survival differences between groups; 3. Univariate and multivariate Cox proportional hazards regression models to identify factors associated with survival. Variables with a P\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in univariate analysis were included in the multivariate analysis (backward stepwise method; statistical significance set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) to determine independent prognostic factors. 4. Additionally, subgroup analyses based on estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) receptor status and treatment modalities were conducted using Cox regression models, and forest plots were generated to visualize the results.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePredictive Modeling\u003c/h3\u003e\n\u003cp\u003eDICOM CT images and dose distribution maps acquired prior to treatment from 149 patients undergoing cranial radiotherapy were utilized for feature extraction. This process was performed using 3D Slicer software (version 5.6.2). A total of 851 original features were extracted from the CT images and dose maps collectively. Subsequently, feature selection was conducted using Least Absolute Shrinkage and Selection Operator (LASSO) regression combined with multivariate Cox regression analysis. Features with a significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were incorporated into the predictive model. To evaluate model performance, multiple metrics were applied, including the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and clinical decision curve analysis (DCA). These evaluations were performed at the 1‑, 2‑, and 3‑year survival timepoints. Finally, a nomogram was developed to visually represent the predictive model.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eBaseline characteristics.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 505 BCBM patients were included in this study, and their baseline characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among them, 293 patients (58.02%) received CRT, while 212 patients (41.98%) did not. The median age was 47 years, and 42.77% of patients were younger than 45 years, suggesting a trend toward younger age at BM diagnosis. Additionally, a relatively high proportion of patients presented with locally advanced disease, and 23.96% had distant metastases at initial diagnosis, with 8.7% having BM at first presentation. According to molecular subtyping based on pathological results, 51.29% of patients were ER+, 36.44% were HER2+, and 14.46% had triple-negative breast cancer (TNBC). In terms of metastatic features, 80.2% of patients had a maximum lesion diameter smaller than 1 cm, and the majority had fewer than 4 metastatic lesions. Regarding treatment, only 8.32% of patients underwent surgical resection of BM, while the majority (62.97%) received chemotherapy. Based on ER and HER2 expression status, some patients also received endocrine therapy (ET) (22.77%) and/or targeted therapy (TT) (24.95%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics of 505 Breast Cancer Brain Metastasis Patients: Comparison Between Radiotherapy and Non-Radiotherapy Groups. HER2: Human Epidermal Growth Factor Receptor 2.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistological grade, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;505)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo brain radiotherapy\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;212)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBrain radiotherapy\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;293)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e304 (60.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e131 (61.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e173 (59.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (1.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e112 (22.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (21.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e67 (22.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83 (16.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33 (15.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50 (17.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e194 (38.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71 (33.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e123 (41.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e259 (51.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e106 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e153 (52.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (16.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17 (5.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eage,n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e216 (42.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86 (40.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e130 (44.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e289 (57.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e126 (59.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e163 (55.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenopausal conditions, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e314 (62.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e119 (56.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e195 (66.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e191 (37.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e93 (43.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e98 (33.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (8.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (7.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28 (9.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e150 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52 (24.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e98 (33.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58 (11.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (12.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31 (10.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110 (21.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44 (20.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66 (22.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e144 (28.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74 (34.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70 (23.89)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75 (14.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (14.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44 (15.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e126 (24.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (21.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80 (27.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88 (17.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (13.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59 (20.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42 (19.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (20.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e114 (22.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64 (30.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50 (17.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e384 (76.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e148 (69.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e236 (80.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121 (23.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64 (30.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57 (19.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological pattern, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-invasive carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (4.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (3.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e453 (89.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e180 (84.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e273 (93.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (6.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (10.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (3.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant chemotherapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e278 (55.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e134 (63.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e144 (49.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e227 (44.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78 (36.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e149 (50.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e183 (36.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70 (33.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e113 (38.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e184 (36.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (26.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128 (43.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e138 (27.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86 (40.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52 (17.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolecular subtyping, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuminal A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44 (8.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (6.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31 (10.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuminal B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e188 (37.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81 (38.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107 (36.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2 overexpression type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e94 (18.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (12.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e67 (22.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriple negative type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73 (14.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (14.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42 (14.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106 (20.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (28.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46 (15.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast Surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e114 (22.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (28.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54 (18.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadical surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e332 (65.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e122 (57.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e210 (71.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast-conserving surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (6.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (6.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17 (5.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28 (5.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (7.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12 (4.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant chemotherapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e194 (38.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e83 (39.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e111 (37.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e311 (61.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e129 (60.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e182 (62.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy for the Breast, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e284 (56.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e127 (59.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e157 (53.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e221 (43.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85 (40.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e136 (46.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaintenance treatment, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e240 (47.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108 (50.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e132 (45.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e119 (23.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49 (23.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70 (23.89)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (6.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37 (12.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine and targeted therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (6.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (5.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21 (7.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64 (12.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (14.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33 (11.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize of brain metastases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e405 (80.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e172 (81.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e233 (79.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;1cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (18.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (20.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of brain metastases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e344 (68.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e160 (75.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e184 (62.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e161 (31.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52 (24.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e109 (37.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeptomeningeal metastases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e455 (90.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e182 (85.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e273 (93.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (14.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (6.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation of brain metastases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupratentorial transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e247 (48.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e116 (54.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e131 (44.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtentorial transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e240 (47.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96 (45.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e144 (49.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (3.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18 (6.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e287 (56.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e139 (65.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e148 (50.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e218 (43.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73 (34.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e145 (49.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocerebral surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e463 (91.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e192 (90.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e271 (92.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (8.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (9.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (7.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine Therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e390 (77.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e173 (81.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e217 (74.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (22.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39 (18.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76 (25.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e187 (37.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96 (45.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91 (31.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e318 (62.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e116 (54.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e202 (68.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted Therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e379 (75.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e176 (83.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e203 (69.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e126 (24.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (16.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90 (30.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAnalysis of survival prognosis.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe median follow-up time for the entire cohort was 40.5 months (95% CI: 37.27\u0026ndash;46.27 months). As shown in the K-M curve in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, the OS for the total population was 20.8 months (95% CI: 18.8\u0026ndash;23.2 months). Univariate and multivariate analyses (Supplementary Table\u0026nbsp;1) indicated that the number of BM, LM, infratentorial metastasis, cranial surgery, CRT, and chemotherapy were associated with OS in BCBM patients. Notably, fewer than 4 brain metastases (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CRT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were identified as independent prognostic factors. Therefore, K-M survival analysis was performed comparing the radiotherapy and non-radiotherapy groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The mOS was 27.0 months (95% CI: 23.33\u0026ndash;30.50 months) in the radiotherapy group (n\u0026thinsp;=\u0026thinsp;293) and 15.10 months (95% CI: 10.97\u0026ndash;17.17 months) in the non-radiotherapy group (n\u0026thinsp;=\u0026thinsp;212), demonstrating a statistically significant difference between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; HR: 0.522; 95% CI: 0.424\u0026ndash;0.632). These results suggest that radiotherapy significantly improves OS in BCBM with a KPS score\u0026thinsp;\u0026ge;\u0026thinsp;70, with particularly pronounced short-term survival benefits.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurther analysis of survival outcomes in the CRT cohort revealed that, as shown in the K-M curve in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, the RT-OS, defined as the time from RT initiation to death or last follow-up, was 22.9 months (95% CI: 20.5\u0026ndash;27.0 months). According to univariate and multivariate analyses (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), factors associated with reduced survival included Ki67\u0026thinsp;\u0026gt;\u0026thinsp;14%, LM, WBRT, ECM, and intracranial progression after RT. The LM (P\u0026thinsp;=\u0026thinsp;0.015), ECM (P\u0026thinsp;=\u0026thinsp;0.015), and intracranial progression after RT (P\u0026thinsp;=\u0026thinsp;0.013) were identified as independent adverse prognostic factors for OS in irradiated patients. Additionally, the RT-PFS was 16.3 months (95% CI: 14.6\u0026ndash;19.17 months; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Notably, LM (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) was an independent adverse prognostic factor for PFS in this population (Supplementary Table\u0026nbsp;2). In the overall cohort, patients with LM had a mOS of 13.43 months (95% CI: 10.37\u0026ndash;19.17 months), while irradiated patients with this condition exhibited a median RT-OS of 12.37 months (95% CI: 7.37\u0026ndash;NA months). These results indicate that RT may not significantly improve survival in patients with LM, however, this conclusion should be interpreted with caution due to the limited sample size, which may introduce bias. Furthermore, patients with stable intracranial disease after RT achieved longer survival, whereas those with ECM experienced poorer overall outcomes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Analysis of Survival in 293 BCBM Patients Treated with RT. HER2: Human Epidermal Growth Factor Receptor 2; SRS: Stereotactic Radiosurgery; WBRT: Whole Brain Radiation Therapy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.832\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.97 (0.73\u0026thinsp;~\u0026thinsp;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological pattern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79 (0.40\u0026thinsp;~\u0026thinsp;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.31 (0.66\u0026thinsp;~\u0026thinsp;2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.40 (0.70\u0026thinsp;~\u0026thinsp;2.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.822\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05 (0.69\u0026thinsp;~\u0026thinsp;1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.30 (0.85\u0026thinsp;~\u0026thinsp;1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKi67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;14%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;14%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.69 (0.48\u0026thinsp;~\u0026thinsp;0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.80 (0.55\u0026thinsp;~\u0026thinsp;1.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.53 (0.31\u0026thinsp;~\u0026thinsp;0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.60 (0.34\u0026thinsp;~\u0026thinsp;1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize of brain metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;1cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;1cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11 (0.76\u0026thinsp;~\u0026thinsp;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.73 (0.87\u0026thinsp;~\u0026thinsp;3.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of brain metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78 (0.55\u0026thinsp;~\u0026thinsp;1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.88 (0.60\u0026thinsp;~\u0026thinsp;1.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59 (1.04\u0026thinsp;~\u0026thinsp;2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.47 (0.95\u0026thinsp;~\u0026thinsp;2.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeptomeningeal metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.03 (1.15\u0026thinsp;~\u0026thinsp;3.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e2.09 (1.15\u0026thinsp;~\u0026thinsp;3.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation of brain metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupratentorial transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.81 (0.44\u0026thinsp;~\u0026thinsp;1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtentorial transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12 (0.62\u0026thinsp;~\u0026thinsp;2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.899\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98 (0.74\u0026thinsp;~\u0026thinsp;1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocerebral surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.58 (0.32\u0026thinsp;~\u0026thinsp;1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.82 (0.43\u0026thinsp;~\u0026thinsp;1.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.88 (0.63\u0026thinsp;~\u0026thinsp;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98 (0.71\u0026thinsp;~\u0026thinsp;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.95 (0.66\u0026thinsp;~\u0026thinsp;1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethods of radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.56 (0.41\u0026thinsp;~\u0026thinsp;0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.75 (0.52\u0026thinsp;~\u0026thinsp;1.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcomitant medications for radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.95 (0.70\u0026thinsp;~\u0026thinsp;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracranial metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.83 (1.25\u0026thinsp;~\u0026thinsp;2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.68 (1.10\u0026thinsp;~\u0026thinsp;2.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracranial progression after radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60 (0.44\u0026thinsp;~\u0026thinsp;0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.67 (0.48\u0026thinsp;~\u0026thinsp;0.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSubgroup Analysis.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAs shown in the forest plot in Supplementary Fig.\u0026nbsp;1A, ET did not significantly improve survival outcomes in ER+ patients after RT. This may be attributed to the fact that the benefits of ET are typically observed in long-term survival, whereas this patient population had relatively shorter OS, thereby limiting observable benefits. Overall, trends suggested that chemotherapy, TT, cranial surgery, or SRS were associated with better survival in these patients, although these differences were not statistically significant. In Supplementary Fig.\u0026nbsp;1B, HER2\u0026thinsp;+\u0026thinsp;patients receiving TT showed improved survival outcomes. This included not only HER2-directed targeted agents but also a small subset of patients who received anti-angiogenic targeted therapy. The results indicate that both types of TT contributed to prolonged survival in BM patients to some extent.\u003c/p\u003e \u003cp\u003e \u003cb\u003eDevelopment of the Predictive Model.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe predictive model was developed by integrating radiomic and dosimetric features with clinical factors from 149 patients. As illustrated in Supplementary Fig.\u0026nbsp;2, all extracted features underwent min-max normalization. Through cross-validation, the parameter λ was adjusted to identify survival-associated features. Feature selection was performed using LASSO regression combined with multivariate Cox analysis, incorporating features with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The optimal λ value (Lambda.1se) was determined to be 0.04882492, resulting in the selection of 9 feature factors in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The coefficients of the feature factors were as follows: 0.201239759、-0.094642364、0.072927215、-0.035393399、-0.228740902、0.189803755、0.089741358、-0.312898484、0.170645305。Ultimately, the aforementioned nine features were incorporated to construct predictive models for 1-year, 2-year, and 3-year survival.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe survival nomogram visually predicts the 1-, 2-, and 3-year OS rates for BCBM patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In terms of performance across the constructed time-dependent predictive models, the 1-year survival model demonstrated the highest predictive accuracy. As shown in Fig.\u0026nbsp;4ABC, time-dependent receiver operating characteristic (ROC) curve analysis revealed AUC values of 0.965, 0.861, and 0.859 for 1-, 2-, and 3-year survival predictions, respectively. Specifically, the 1-year survival prediction showed a sensitivity of 1.000, specificity of 0.829, and accuracy of 0.832; the 2-year prediction had a sensitivity of 1.000, specificity of 0.681, and accuracy of 0.711; and the 3-year prediction achieved a sensitivity of 0.973, specificity of 0.455, and accuracy of 0.584. Furthermore, the calibration curves for 1-, 2-, and 3-year survival predictions (Fig.\u0026nbsp;4DEF) indicated minimal deviation between predicted and observed outcomes, suggesting good model reliability. In conclusion, the integration of clinical factors, radiotherapy radiomics, and radiodosimetric features holds significant clinical utility for predicting 1-, 2-, and 3-year survival in BCBM patients. This approach provides valuable guidance for improving outcomes in this population; however, the predictive performance gradually decreases as the survival time frame extends.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study, based on single-center data, analyzed the prognosis of BCBM patients. The results indicate that CRT is associated with a significant survival benefit in BCBM patients with a KPS score\u0026thinsp;\u0026ge;\u0026thinsp;70. The overall survival observed in our cohort is consistent with current published findings (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). After the development of BM, survival in BM patients is primarily influenced by the characteristics of the BM and the treatment strategies employed (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). RT, as one of the main treatment modalities for BM, improves local control rates (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Importantly, our study demonstrates that RT not only enhances local control but also significantly improves OS in irradiated patients. Furthermore, patients who achieved stable intracranial disease after RT showed pronounced benefits in long-term survival.\u003c/p\u003e \u003cp\u003eSystemic therapy also plays a crucial role in the long-term survival of BCBM patients. Currently, the majority of patients receive chemotherapy for disease control, while only a minority undergo ET or TT (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). For HER2\u0026thinsp;+\u0026thinsp;patients, existing studies have demonstrated that TT can prolong survival in those with BM (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A real-world multicenter study (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) indicated that patients receiving CRT combined with pyrotinib achieved improved survival outcomes. Additionally, a phase 3 trial showed (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) that pyrotinib plus capecitabine significantly improved PFS compared to lapatinib plus capecitabine, providing an alternative treatment option for HER2\u0026thinsp;+\u0026thinsp;metastatic BC patients after trastuzumab and chemotherapy. In the present study, although the use of TT after BM did not demonstrate a statistically significant improvement in OS or PFS among irradiated patients overall, subgroup analysis revealed a survival benefit in HER2\u0026thinsp;+\u0026thinsp;patients who received TT alongside CRT. Based on these findings, HER2\u0026thinsp;+\u0026thinsp;BCBM patients with good performance status are likely to achieve prolonged survival through a combination of CRT and TT.\u003c/p\u003e \u003cp\u003eIn this study, only 50 (9.9%) BC patients were diagnosed with LM via MRI. Among these LM patients, 30 (60%) received RT; however, they still exhibited poor survival outcomes despite this intervention. Previous studies have similarly reported significantly worse prognosis in patients with LM (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). On one hand, current imaging techniques require further improvement to enable earlier detection of LM (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). On the other hand, effective treatment strategies for LM remain limited. The main approach involves a combination of systemic therapy and local treatment; however, the efficacy of systemic agents is often constrained by the BBB (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Although recent studies suggest that small-molecule targeted therapies may improve survival in HER2\u0026thinsp;+\u0026thinsp;BC patients with LM (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), no clinical trials have yet explored whether combining RT with TT provides additional benefits for this specific population. Further investigation is needed to address this question.\u003c/p\u003e \u003cp\u003ePredictive models utilize existing data to estimate an individual's risk of developing a disease or experiencing a specific future outcome, and they already offer valuable guidance in clinical practice. For instance, a study by Josef A. Buchner et al. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) employed radiomics to predict local control in BM patients following postoperative stereotactic radiotherapy. Similarly, another study based on a prospective trial predicted treatment response and overall survival in breast cancer brain metastasis patients treated with stereotactic radiosurgery (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). While these models demonstrated good predictive value, they incorporated a relatively limited set of variables. Currently, many studies integrate clinical and radiomic features to predict local control after RT for BM, and the combination of these factors has been shown to significantly enhance model performance (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). The present study is the first to incorporate clinical variables, radiotherapy imaging features, and radiodosimetric parameters into a unified predictive model for survival prognosis in BCBM patients. The model validation results indicate strong predictive accuracy, suggesting its potential utility in guiding clinical management and improving survival outcomes for this patient population.\u003c/p\u003e \u003cp\u003eThis study has several inherent limitations. First, as a single-center retrospective analysis, the results are subject to potential selection bias, which may affect the accuracy and generalizability of the findings. Second, the study spans a relatively long period, during which changes in systemic treatment strategies and advancements in radiotherapy techniques may have influenced patient outcomes. These temporal variations could introduce confounding effects that impact the interpretation of the data and the validity of the conclusions. Finally, the sample size used to develop the predictive model was relatively small. Therefore, the conclusions require validation in larger, multicenter prospective cohort studies, as well as further verification using external datasets or prospective data.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, BCBM patients with good performance status can achieve long-term survival benefits from CRT, particularly when local control of intracranial lesions is maintained, which is associated with significantly prolonged OS. However, the development of LM leads to a substantially worse overall prognosis. Therefore, early detection and timely intervention for LM are critically important. Our predictive model demonstrates strong performance in estimating patient prognosis. In the future, incorporating additional relevant factors could further enhance its accuracy, ultimately enabling more effective prediction of outcomes in BCBM patients, guiding clinical decision-making, and thereby contributing to improved survival and patient support.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFull title\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eradiotherapy\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ebreast cancer patients with brain metastases\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBCBM\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKarnofsky Performance Status\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKPS\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ecraniocerebral radiotherapy\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKaplan-Meier\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eK-M\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emedian overall survival\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emOS\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eleptomeningeal metastasis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLM\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eextracranial metastasis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eECM\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003earea under curve\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAUC\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBreast cancer\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBC\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ebrain metastasis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBM\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003estereotactic radiosurgery\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSRS\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAmerican Society of Clinical Oncology\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eASCO\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAmerican Society for Therapeutic Radiology and Oncology\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eASTRO\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ewhole-brain radiotherapy\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWBRT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eComputed Tomography\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMagnetic Resonance Imaging\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMRI\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRadiation-specific overall survival\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRT-OS\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRadiation-specific progression-free survival\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRT-PFS\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLeast Absolute Shrinkage and Selection Operator\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLASSO\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ereceiver operating characteristic\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eROC\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eclinical decision curve analysis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDCA\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003etriple-negative breast cancer\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTNBC\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eendocrine therapy\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eET\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003etargeted therapy\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHuman Epidermal Growth Factor Receptor 2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHER2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eestrogen receptor\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Yunnan Cancer Hospital (approval number: SLKYLX2025-219), and the experimental procedures were conducted in accordance with the relevant regulations and in strict compliance with the Declaration of Helsinki. Informed consent to participate was obtained from all participants also.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMan Li (First Author): Conceptualization, Validation, Formal analysis, Investigation, Data Curation, Writing-Original Draft. Yuchen, Ge: Formal analysis, Investigation, Writing-Review \u0026amp; Editing. Tao Wei: Software, Data Curation, Methodology. Yifan Lei: Software, Data Curation. Yunyan Yang: Investigation, Data Curation. Mingrui Zhao: Data Curation, Visualization. Bo Li: Data Curation, Methodology. Wenhui Li (Corresponding author): Resources, Project administration, Conceptualisation, Writing - Review \u0026amp; Editing, Funding acquisition. Li Wang (Corresponding author): Resources, Conceptualisation, Project administration, Writing - Review \u0026amp; Editing, Funding acquisition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information and Acknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was financially supported by the National Natural Science Foundation of China (82460576), Xingdian Talents Support Program for young Talents (XDYC-QNRC-2023-0189) and Yunnan Provincial Health Commission Medical Reserve Talent Training Program(H2024022).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGiaquinto AN, Sung H, Newman LA, Freedman RA, Smith RA, Star J, et al. Breast cancer statistics 2024. Cancer J Clin. 2024;74(6):477\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang R, Zhu Y, Liu X, Liao X, He J, Niu L. The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19(1):1091.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMashiach E, Alzate JD, De Nigris Vasconcellos F, Bernstein K, Donahue BR, Schnurman Z, et al. Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies. Neurosurgery. 2024;94(1):154\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo J, Ren A, Si D, Yang J, Xu D, Li N. Drug treatment of breast cancer brain metastases: progress and challenges. Discover Oncol. 2025;16(1):1025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMashiach E, Alzate JD, De Nigris Vasconcellos F, Adams S, Santhumayor B, Meng Y, et al. Improved outcomes for triple negative breast cancer brain metastases patients after stereotactic radiosurgery and new systemic approaches. J Neurooncol. 2024;168(1):99\u0026ndash;109.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmeida ND, Kuo C, Schrand TV, Rupp J, Madhugiri VS, Goulenko V et al. Stereotactic Radiosurgery for Intracranial Breast Metastases: A Systematic Review and Meta-Analysis. Cancers. 2024;16(20).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEstermann A, Schneider C, Zimmermann F, Papachristofilou A, Finazzi T. Whole brain radiation therapy for patients with brain metastases: survival outcomes and prognostic factors in a contemporary institutional series. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al]. 2024;200(11):942\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreeman M, Ennis M, Jerzak KJ. Karnofsky Performance Status (KPS)\u0026thinsp;\u0026le;\u0026thinsp;60 Is Strongly Associated With Shorter Brain-Specific Progression-Free Survival Among Patients With Metastatic Breast Cancer With Brain Metastases. Front Oncol. 2022;12:867462.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNatesan D, Carpenter DJ, Giles W, Oyekunle T, Niedzwiecki D, Reitman ZJ, et al. Clinical Factors Associated With 30-Day Mortality Among Patients Undergoing Radiation Therapy for Brain Metastases. Adv radiation Oncol. 2023;8(4):101211.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S, Cahill D, et al. Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(5):492\u0026ndash;516.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchiff D, Messersmith H, Brastianos PK, Brown PD, Burri S, Dunn IF, et al. Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(20):2271\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGondi V, Bauman G, Bradfield L, Burri SH, Cabrera AR, Cunningham DA, et al. Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. Practical radiation Oncol. 2022;12(4):265\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosen J, Werner JM, Ceccon GS, Rosen EK, Wollring MM, Stetter I, et al. MRI and (18)F-FET PET for Multimodal Treatment Monitoring in Patients with Brain Metastases: A Cost-Effectiveness Analysis. Journal of nuclear medicine: official publication. Soc Nuclear Med. 2024;65(6):838\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYan M, Ouyang Q, Sun T, Niu L, Yang J, Li L, et al. Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial. EClinicalMedicine. 2024;76:102837.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X, Sun Y, Tang L, Li Y, Yang X. Treatment of metastatic breast cancer by stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS). Discover Oncol. 2024;15(1):733.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrinda T, Aizer AA, Lin NU, Sammons SL. Central Nervous System Metastases in Breast Cancer. Curr Treat Options Oncol. 2025;26(1):14\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026eacute;court S, Cheymol C, Cren PY, Mouttet-Audouard R. [Brain metastases in breast cancer: Diagnosis and management]. Bulletin du cancer; 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Schie P, Huisman RG, Wiersma T, Knegjens JL, Navran A, Brandsma D, et al. Local control and toxicity after stereotactic radiotherapy in brain metastases patients and the impact of novel systemic treatments. Radiotherapy oncology: J Eur Soc Therapeutic Radiol Oncol. 2024;200:110540.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFabian A, Buergy D, Weykamp F, H\u0026ouml;rner-Rieber J, Bernhardt D, Boda-Heggemann J, et al. Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study. Clin Exp Metastasis. 2024;42(1):6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarrone O, Ruatta F, Rea CG, Denaro N, Ghidini M, Cauchi C et al. Current Evidence in the Systemic Treatment of Brain Metastases from Breast Cancer and Future Perspectives on New Drugs, Combinations and Administration Routes: A Narrative Review. Cancers. 2024;16(24).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang J, Sun S, Tan Q, Zheng F, Zhou D, Man X, et al. Effectiveness and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-Positive Breast Cancer Patients with Brain Metastases: A Multicenter Real-World Study. Clin Breast Cancer. 2024;24(6):e509. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e-e18.e1\u003c/span\u003e\u003cspan address=\"http://-e18.e1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(3):351\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorikawa A, Jordan L, Rozner R, Patil S, Boire A, Pentsova E, et al. Characteristics and Outcomes of Patients With Breast Cancer With Leptomeningeal Metastasis. Clin Breast Cancer. 2017;17(1):23\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuppert LA, Fisch S, Tsopurashvili E, Somepalle SS, Salans M, Vasudevan HN, et al. Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study. Breast Cancer Res Treat. 2024;206(3):625\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen-Nowak AJ, Hill VB, Kumthekar P. Diagnostics and Screening in Breast Cancer with Brain and Leptomeningeal Metastasis: A Review of the Literature. Cancers. 2024;16:21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLouveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartsch R, Jerzak KJ, Larrouquere L, M\u0026uuml;ller V, Le Rhun E. Pharmacotherapy for leptomeningeal disease in breast cancer. Cancer Treat Rev. 2024;122:102653.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eId Said B, Jerzak KJ, Chen H, Moravan V, Warner E, Myrehaug S, et al. Survival outcomes among patients with breast cancer and leptomeningeal disease. Sci Rep. 2025;15(1):24170.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuchner JA, Kofler F, Mayinger M, Christ SM, Brunner TB, Wittig A, et al. Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy. Neurooncology. 2024;26(9):1638\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsos K, Michalopoulos G, D'Ambrosio AL, Cobb WS, Grills IS, McInerney J et al. Predictors of treatment response and overall survival in patients with breast cancer brain metastases treated with stereotactic radiosurgery: a prospective study using the NeuroPoint Alliance SRS Registry. J Neurosurg. 2025:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanakarajan H, De Baene W, Hanssens P, Sitskoorn M. Predicting local control of brain metastases after stereotactic radiotherapy with clinical, radiomics and deep learning features. Radiation Oncol (London England). 2024;19(1):182.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVolovăț CC, Buzea CG, Boboc DI, Ostafe MR, Agop M, Ochiuz L et al. Hybrid Deep Learning for Survival Prediction in Brain Metastases Using Multimodal MRI and Clinical Data. Diagnostics (Basel Switzerland). 2025;15(10).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer brain metastases, Craniocerebral radiotherapy, Survival outcomes, Predictive modeling, Radiomics and radiodosomics","lastPublishedDoi":"10.21203/rs.3.rs-9149925/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9149925/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWith advances in systemic therapy, survival has improved in patients with breast cancer brain metastases (BCBM). Radiotherapy (RT), as a local treatment, further contributes to this improvement. This study investigates the prognostic factors for survival in BCBM patients with a Karnofsky Performance Status (KPS) score\u0026thinsp;\u0026ge;\u0026thinsp;70 who underwent craniocerebral radiotherapy (CRT).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 505 patients with BCBM diagnosed in our hospital from January 2017 to December 2023 were retrospectively explored. Subsequently, Kaplan-Meier method (K-M method) was used to analyze overall survival (OS) and progression-free survival (PFS). Additionally, Clinical data were collected, radiomics and dosimetric factors were extracted for univariate and multivariate model analysis, and a survival prediction model was established.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median overall survival (mOS) of the 505 BCBM patients was 20.8 months (95% CI 18.8\u0026ndash;23.2 months). Multivariate analysis identified the number (\u0026le;\u0026thinsp;4) of brain metastases (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CRT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as independent prognostic factors. Specifically, the median OS in the CRT group (n\u0026thinsp;=\u0026thinsp;293) was 27.0 months (95% CI 23.33\u0026ndash;30.50 months), which was significantly longer than that of the non-radiotherapy group (n\u0026thinsp;=\u0026thinsp;212), which had a median OS of 15.10 months (95% CI 10.97\u0026ndash;17.17 months). A significant survival difference was observed between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, HR 0.522, 95% CI 0.424\u0026ndash;0.632). Furthermore, Multivariate analysis revealed that leptomeningeal metastasis (LM) (P\u0026thinsp;=\u0026thinsp;0.015), extracranial metastasis (P\u0026thinsp;=\u0026thinsp;0.015), and intracranial progression after RT (P\u0026thinsp;=\u0026thinsp;0.013) were independent adverse prognostic factors for OS in patients receiving CRT. Additionally, the median progression-free survival (PFS) in the radiotherapy group was 16.3 months (95% CI 14.6\u0026ndash;19.17 months), with LM (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) identified as an independent adverse prognostic factor for PFS. In the subgroup analysis, patients with positive expression of human epidermal growth factor receptor 2 (HER2) had a better survival benefit when treated with targeted therapy (TT) (P\u0026thinsp;=\u0026thinsp;0.021). Finally, a predictive model incorporating radiomic and radiodosimetric features (n\u0026thinsp;=\u0026thinsp;149) was developed and showed excellent performance in predicting 1-, 2-, and 3-year survival, with area under curve (AUC) values of 0.965, 0.861, and 0.859, respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFor BCBM patients with a KPS\u0026thinsp;\u0026ge;\u0026thinsp;70, CRT is associated with a significant survival benefit. However, the development of LM remains a major adverse factor leading to poorer overall prognosis. Besides, the integration of radiomic and radiodosimetric features into predictive models demonstrates strong potential for accurately estimating prognosis. These findings suggest that such models could enhance clinical decision-making, ultimately supporting improved patient outcomes.\u003c/p\u003e","manuscriptTitle":"Prognostic Factors Analysis in Breast Cancer Patients with Brain Metastases: Identification of Key Determinants of Survival1","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 02:35:58","doi":"10.21203/rs.3.rs-9149925/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"77025587118017444587258115487727238443","date":"2026-05-08T07:41:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-06T06:02:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-19T07:30:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-19T07:30:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Radiation Oncology","date":"2026-03-17T14:18:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"891e439a-d147-4e70-af43-dd6e0cf6026d","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"77025587118017444587258115487727238443","date":"2026-05-08T07:41:11+00:00","index":61,"fulltext":""},{"type":"reviewersInvited","content":"47","date":"2026-05-06T06:02:50+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T02:35:58+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 02:35:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9149925","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9149925","identity":"rs-9149925","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}