Abstract
This study aims to investigate the clinicopathological features and prognosis of brain metastasis in non-small cell lung cancer (NSCLC). A total of 80 patients with brain metastases from NSCLC admitted to our hospital from Jan 2021 to Dec 2023 were retrospectively selected as patients in the brain metastasis group. One hundred patients with NSCLC who were admitted during the same period were selected as patients with non-brain metastasis. The relationship between different clinicopathological characteristics of lung cancer and brain metastasis was analyzed, the survival curves of patients in the 2 groups were compared, and the prognostic impact was analyzed by univariate and multifactor Logistics regression. The differences were statistically significant among histological types, metastasis time, and gene mutations (P < .05). The results of single and multivariate Logistics regression analysis showed that age, smoking history, T-stage, and tumor node metastasis stage were independent factors influencing the prognostic outcome of patients with brain metastasis of NSCLC (P < .05). Age, smoking history, T-stage, and tumor node metastasis stage are independent influencing factors on the prognosis of patients with brain metastases from NSCLC, and intervention should be taken based on the influencing factors.
Keywords: brain metastases, non-small cell lung cancer (NSCLC), pathological features, prognosis, risk factors
1. Introduction
Non-small cell lung cancer (NSCLC) covering a variety of histological subtypes.[1] When NSCLC enters the advanced stage, cancer cells may spread to other parts of the body through various pathways, among which brain metastasis is a common and serious complication. Brain metastasis means that cancer cells have invaded the brain through blood circulation and other pathways, forming new tumor foci.[2–4] After brain metastases, patients may experience a range of neurological-related symptoms, including but not limited to: persistent and intense headache, nausea, and vomiting (possibly projectile), limb movement impairment, language dysfunction, cognitive decline, confusion, and possibly even coma.[5] Therefore, it is important to study the clinicopathological features and prognostic factors of brain metastasis in NSCLC for improving the quality of life and prolonging survival. This study analyzed the clinicopathological characteristics and prognosis of brain metastasis in NSCLC, providing a reference for clinical practice.
2. Subjects and methods
2.1. Research subjects
A total of 80 patients with NSCLC with brain metastases admitted to our hospital from Jan 2021 to Dec 2023, were retrospectively selected as the brain metastases group. A total of 100 patients with NSCLC without brain metastases admitted at the same time were selected as the non-brain metastasis group. The clinical data collection and retrospective analyses were approved by the Ethic Committee of Affiliated Jinhua Hospital, Zhejiang University School of Medicine (No. 2024LunShenNO20). Patient consents were waived since the present study did not include personal details.
Inclusion criteria: all patients met the clinical diagnosis of NSCLC.[6] All patients underwent low-dose computed tomography lung cancer screening with 16 or more rows of spiral CT and were diagnosed. The long diameter of nodules < 10 mm was expressed by the average of the overall long and short axis diameters of the nodules. The long and short diameters of nodules ≥10 mm needed to be measured and recorded separately. All patients in the brain metastasis group were consistent with the clinical diagnosis of brain metastases from NSCLC; none of the patients had received antitumor therapy before admission.
Exclusion criteria: patients with chronic obstructive pulmonary disease, tuberculosis, and other lung diseases. patients with mental disorders. patients with abnormal immune system.
2.2. Methods
All patients were followed up for 12 months after surgical treatment in our hospital. If the survival time of patients was <6 months or the quality of life of patients was poor, with serious neurological symptoms such as headache, nausea, vomiting, limb and language dysfunction, obnubilation, and even coma, the prognosis was poor.
2.3. Observation indicators
To analyze the relationship between different clinicopathological features of lung cancer and brain metastasis. The survival curves of the 2 groups were compared. Patients were followed up for 12 months after surgery. The difference in patient survival is defined as the difference between death or poor prognosis and good prognosis. Overall survival (OS) was the date from resection of brain metastases to death or last follow-up.
2.4. Statistical analysis
Experimental data were analyzed in SPSS 27.0. Normally distributed measures were presented as mean ± SD, an independent-samples t test for comparison. Enumeration data were reported as counts or percentages, analyzed by χ2 or Fisher’s exact test. Factors influencing NSCLC brain metastasis prognosis were explored using univariate and binary logistic regression, with statistical significance set at P < .05.
3. Results
3.1. Relationship between different clinicopathological features of lung cancer and brain metastasis
There were significant differences in histological type, occurrence time of metastasis and gene mutation (P < .05), as shown in Table 1.
Table 1.
Relationship between different clinicopathological features of lung cancer and brain metastasis.
| Item | Brain metastasis group (n = 80) | Non-brain metastasis group (n = 100) | X2 value | P value | |
|---|---|---|---|---|---|
| Sex | Male | 45 | 52 | 0.323 | .851 |
| Female | 35 | 48 | |||
| Age (yr) | 18–60 | 27 | 30 | 0.289 | .866 |
| >60 | 53 | 70 | |||
| BMI | <22 | 50 | 68 | 0.595 | .743 |
| ≥22 | 30 | 32 | |||
| Type of histology | Adenocarcinoma | 73 | 50 | 35.15 | <.001 |
| Squamous cell carcinoma | 4 | 35 | |||
| Adenosquamous carcinoma | 3 | 15 | |||
| Smoking | Yes | 58 | 75 | 0.144 | .931 |
| No | 22 | 25 | |||
| Tumor size | ≥5 cm | 64 | 75 | 0.632 | .729 |
| <5 cm | 16 | 25 | |||
| Degree of differentiation | Low | 56 | 68 | 0083 | .959 |
| Medium–high | 24 | 32 | |||
| Transfer occurrence time | No | 0 | 20 | 23.34 | <.001 |
| Simultaneous with primary lesion | 64 | 74 | |||
| At different time from the primary lesion | 16 | 6 | |||
| Gene mutation | EGFR mutation | 37 | 45 | 11.10 | .049 |
| ALK translocation | 7 | 7 | |||
| Negative driver gene | 31 | 30 | |||
| ROS-1 mutation | 4 | 3 | |||
| Miscellaneous | 1 | 15 | |||
BMI = body mass index, ALK = anaplastic lymphoma kinase, EGFR = epidermal growth factor receptor, ROS-1 = c-ros oncogene 1.
3.2. Survival curve of patients in the 2 groups
None of the 180 patients were lost to follow-up. The median OS was 5 months (95% CI: 1.124–3.746) in the brain metastasis group and 9 months (95% CI: 0.267–0.806) in the non-brain metastasis group, with statistically significant differences (P < .05), as shown in Figure 1.
Figure 1.
Survival curves.
3.3. Comparison of general data between 2 groups of patients
The univariate results showed that there was no statistically significant difference in age, smoking history, T-stage and tumor node metastasis (TNM) stage (Table 2). The difference was statistically significant (P < .05).
Table 2.
Comparison of general data between 2 groups of patients.
| Indicator | Good prognosis group (n = 48) | Poor prognosis group (n = 32) | t/χ2 value | P value | |
|---|---|---|---|---|---|
| Age (yr) | 54.22 ± 4.21 | 62.48 ± 3.71 | 9.006 | .000 | |
| Sex | Male | 24 | 21 | 1.905 | .386 |
| Female | 24 | 11 | |||
| BMI (kg/m2) | 22.48 ± 2.22 | 22.07 ± 2.19 | 0.814 | .418 | |
| Smoking history | Yes | 30 | 28 | 6.019 | .049 |
| N/A | 18 | 4 | |||
| Hypertension | Yes | 10 | 8 | 0.191 | .909 |
| N/A | 38 | 24 | |||
| Diabetes | Yes | 5 | 3 | 0.049 | .976 |
| N/A | 43 | 30 | |||
| Tumor location | Right upper lung | 12 | 8 | 0.160 | .999 |
| Right middle lung | 3 | 2 | |||
| Right lower lung | 9 | 7 | |||
| Left upper lung | 17 | 11 | |||
| Left upper lung | 7 | 4 | |||
| T stageing | T1 | 5 | 5 | 10.65 | .031 |
| T2 | 35 | 12 | |||
| T3 | 5 | 10 | |||
| T4 | 3 | 5 | |||
| TNM staging | I | 21 | 5 | 8.011 | .046 |
| II | 17 | 20 | |||
| III | 10 | 5 |
BMI = body mass index, TNM = tumor node metastasis.
3.4. Multivariate logistic regression analysis of prognostic factors in patients with brain metastases from NSCLC
Age, smoking history, T-stage and TNM stage were assigned as independent variables (actual values substituted), and prognostic outcome was used as dependent variable for analysis (poor prognosis = 1, good prognosis = 0). The results of multivariate Logistics regression analysis showed that age, smoking history, T-stage, and TNM stage were independent influencing factors for prognostic outcomes of patients with brain metastases from NSCLC (P < .05), as shown in Table 3.
Table 3.
Multivariate Logistics regression analysis of prognostic factors in patients with brain metastases from non-small cell lung cancer.
| Risk factors | Β value | SE value | Ward value | OR value | 95% CI | P value |
|---|---|---|---|---|---|---|
| Age | 1.149 | 0.495 | 5.385 | 3.154 | 1.195–8.322 | <.001 |
| Smoking history | 1.079 | 0.452 | 5.700 | 2.942 | 1.213–7.135 | <.001 |
| T staging | 1.155 | 0.521 | 4.917 | 3.175 | 1.144–8.815 | <.001 |
| TNM staging | 1.126 | 0.564 | 3.987 | 3.084 | 1.021–9.315 | <.001 |
TNM = tumor node metastasis.
4. Discussion
As 1 of the main types of lung cancer, NSCLC has high morbidity and mortality. With the advancement of lung cancer treatment technology, the survival time of patients has been prolonged to a certain extent, but brain metastases are still a key factor affecting the quality of life and prognosis of NSCLC patients.[7] The purpose of this article is to explore the clinicopathological features and prognosis of brain metastasis in NSCLC by retrospective analysis, to provide theoretical basis for clinical treatment.
In NSCLC, adenocarcinoma and squamous cell carcinoma are the 2 main histological types. Investigation concurred with prior research, revealing a higher incidence of brain metastasis among patients with adenocarcinoma compared to those with squamous cell carcinoma.[8] The biological characteristics of adenocarcinoma make it easier to cross the blood-brain barrier, which leads to brain metastasis. Therefore, patients with adenocarcinoma should be highly alert to the possibility of brain metastases and take corresponding preventive measures.[9,10] The study results also found that the occurrence time of brain metastasis in NSCLC was closely related to the prognosis of patients. The earlier the metastasis occurs, the worse the prognosis of patients. This may be related to the rapid growth and spread of early brain metastases, resulting in poor efficacy.[11] Therefore, for patients with NSCLC, brain metastasis screening should be performed as early as possible to detect and treat brain metastases in a timely manner. In recent years, genetic testing technology has been more and more widely used in the diagnosis and treatment of lung cancer. The results of this study show that some patients with NSCLC have gene mutations, which are closely related to brain metastases. For example, anaplastic lymphoma kinase gene fusion and epidermal growth factor receptor mutation are associated with the occurrence of NSCLC brain metastases. The discovery of these gene mutations provides new targets for the treatment of NSCLC brain metastases and provides a theoretical basis for gene targeted therapy.[12,13]
The study results showed that there were no lost to follow-up cases in 180 patients. The median OS was 5 months in the brain metastasis group and 9 months in the non-brain metastasis group, with a statistically significant difference. The data of the study showed that among 180 NSCLC, there were no lost to follow-up cases, which provided a solid basis for our analysis. However, survival differences between the 2 groups were apparent. This significant difference not only reflects the severe negative impact of brain metastases on the prognosis of NSCLC patients, but also highlights the extreme risk of brain metastases in the course of NSCLC. The presence of brain metastases undoubtedly increases the difficulty in the treatment of NSCLC.[14] On the 1 hand, brain metastases tend to grow and spread rapidly, which makes traditional chemotherapy and radiotherapy have limited efficacy and great side effects. On the other hand, brain metastases may lead to a series of serious neurological symptoms in patients, such as headache, nausea, vomiting, limb weakness, and slurred speech. These symptoms not only greatly reduce the quality of life of patients, but also endanger their lives.[15] This means that the clinical need to combine the specific situation of patients, chemotherapy, radiotherapy, surgery, and other treatment methods. Chemotherapy and radiotherapy can inhibit the growth and spread of tumor cells, while surgery can directly remove brain metastases and alleviate patients’ symptoms.[16] Comprehensive treatment can effectively slow down the growth and spread of brain metastases, improve therapeutic efficacy, thus prolonging the survival time of patients. In addition, with the deepening of medical research, targeted therapy and immunotherapy have gradually become important means for the treatment of brain metastases from NSCLC. According to the gene mutation and immune status of patients, corresponding targeted drugs or immunotherapy can be used to improve the pertinence and effectiveness of treatment.[17,18] However, for patients with advanced NSCLC brain metastases, the treatment difficulty increases accordingly due to the severity of the disease. In such cases, emphasis should be placed on improving the patient’s quality of life and using palliative care and nursing approaches. Palliative care aims to alleviate symptoms and reduce suffering, while nursing can provide psychological support and nutritional support to help patients overcome difficulties.[19]
Further, by univariate and multivariate Logistical regression analysis, this study found that age, smoking history, T-stage, and TNM stage were independent factors influencing the prognostic outcomes of patients with brain metastases NSCLC. The older the age, the worse the patient’s physical function, the less tolerance to treatment and naturally a poorer prognosis. Smoking history is closely related to the occurrence of lung cancer, and the incidence and mortality of lung cancer in smokers are higher than those in nonsmokers. T staging and TNM staging are important indicators for assessing the severity of lung cancer. The higher the stage, the wider the tumor invasion and the worse the prognosis. For the treatment strategy of patients with brain metastases from NSCLC, this study suggests that local therapy for brain metastases should be combined based on systemic therapy. Systemic treatment includes chemotherapy, targeted therapy, etc which can inhibit the growth and spread of tumor cells; local treatment includes surgical resection, whole brain radiotherapy, stereotactic radiosurgery, etc which can directly act on brain metastases, reduce patient symptoms, and improve therapeutic efficacy.[20] At the same time, for patients with genetic mutations, gene targeted therapy can be considered to further improve the efficacy of treatment.
This study not only revealed the clinicopathological characteristics of brain metastases from NSCLC through retrospective analysis, but also innovatively combined single and multivariate Logistics regression analysis to identify age, smoking history, T-stage, and TNM stage as independent prognostic factors. This discovery provides a more accurate prognostic assessment tool for clinical practice and helps formulate personalized treatment plans. In addition, the study also compared the median OS between the brain metastasis group and the non-brain metastasis group, further emphasizing the impact of brain metastasis on survival, pointing out the direction for subsequent research, and providing new perspectives and strategies for clinical intervention.
We found that there were differences in histological type, occurrence time of metastasis, age, smoking history, T-stage, and TNM stage are independent factors influencing the prognosis of patients with brain metastases from NSCLC. In view of these influencing factors, corresponding intervention measures should be taken to improve the prognosis of patients with NSCLC brain metastases. Although the research has achieved some results, there are still some limitations. First, this is a retrospective study and there may be information gaps or data biases. Second, the accuracy of some results may be compromised due to limited sample size. Future studies may expand the sample size and adopt prospective research methods to further improve the accuracy and reliability of the study. At the same time, multidisciplinary means such as molecular biology and imaging can be combined to deeply explore the pathogenesis and treatment strategy of brain metastases in NSCLC.
In conclusion, NSCLC brain metastases have a serious negative impact on the prognosis of patients. In order to improve the survival and quality of life of patients with NSCLC brain metastases, more active and effective treatment measures should be taken, and individualized treatment should be carried out in combination with the specific conditions of patients. At the same time, new treatment methods and technologies need to be further explored to bring better therapeutic effects for patients with NSCLC brain metastases.
Acknowledgments
The authors are grateful to all participants in the present study.
Author contributions
Conceptualization: Xiaodan Fu, Qingwei Liu, Jinli Jia, Minyuan Wang.
Formal analysis: Xiaodan Fu, Qingwei Liu, Jinli Jia, Minyuan Wang.
Investigation: Xiaodan Fu, Qingwei Liu, Jinli Jia, Minyuan Wang.
Methodology: Xiaodan Fu, Qingwei Liu, Jinli Jia, Minyuan Wang.
Writing – original draft: Xiaodan Fu.
Abbreviation:
- NSCLC
- non-small cell lung cancer
- OS
- overall survival
- TNM
- tumor node metastasis
The clinical data collection and retrospective analyses were approved by the Ethic Committee of Affiliated Jinhua Hospital, Zhejiang University School of Medicine (No. 2024LunShenNO20). Patient consents were waived since the present study did not include personal details.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Fu X, Liu Q, Jia J, Wang M. Clinicopathological characteristics and prognosis of brain metastasis in non-small cell lung cancer: A retrospective study. Medicine 2026;105:7(e46584).
Contributor Information
Qingwei Liu, Email: Weiweige1980@163.com.
Jinli Jia, Email: Xiaoxiaozao2021@163.com.
Minyuan Wang, Email: Jingbingbing1990@163.com.
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