Patterns and risk factors of intracranial recurrence after surgical resection of brain metastases from malignant tumors

恶性肿瘤脑转移瘤手术切除后颅内复发的模式和危险因素

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Abstract

BACKGROUND: The incidence of brain metastases is increasing, and surgical resection remains a key treatment modality. However, postoperative intracranial recurrence - including local recurrence (LR), distant brain recurrence (DBR), and leptomeningeal disease (LMD) - significantly impacts patient prognosis. Previous studies have predominantly focused on single tumor types and lacked systematic analyses of recurrence patterns and risk factors. OBJECTIVES: This study aimed to investigate the incidence, temporal distribution, and independent risk factors associated with distinct postoperative recurrence patterns. METHODS: Demographic, imaging, surgical, pathological, and post-treatment data from 198 patients who underwent resection of brain metastases were retrospectively analyzed. Kaplan-Meier and Fine-Gray models were used to evaluate recurrence timing, and a multinomial logistic regression model (using the non-recurrence group as reference) was applied to identify risk factors. A cause-specific Cox proportional hazards model was further employed to analyze recurrence timing while considering death as a competing risk. RESULTS: Intracranial recurrence occurred in 119 patients (60.1%). LR was the most frequent type (47.1%), whereas LMD developed latest (median 14.6 vs. 9.1 months for LR, P<0.05). Independent risk factors for LR included tumor size >3 cm, proximity to the ventricle or dura mater, intraoperative tumor rupture, and omission of cavity radiotherapy. DBR was associated with ≥3 brain metastases, extracranial metastases, and lack of whole-brain radiotherapy. LMD was linked to primary breast cancer, intraoperative rupture, meningeal invasion, and delayed radiotherapy (≥4 weeks). The areas under the curve (AUCs) of predictive models were 0.78 for LR, 0.74 for DBR, and 0.81 for LMD. Stratified analysis by tumor type revealed that lung cancer most commonly exhibited LR (30.0%), followed by DBR (21.7%), with LMD being least frequent (5.8%); breast cancer demonstrated the highest incidence of LMD (21.4%). Multivariable analysis identified tumor size >3 cm and ventricular/dural proximity as independent risk factors for LR in lung cancer, while ≥3 metastases predicted DBR. In breast cancer, human epidermal growth factor receptor 2 positivity and delayed radiotherapy (≥4 weeks) were associated with LMD. Predictive model AUCs ranged from 0.65 to 0.83, indicating that recurrence patterns and risk factors are tumor type-specific. CONCLUSION: Postoperative intracranial recurrence after surgical resection of brain metastasis demonstrates distinct incidence rates, temporal profiles, and independent risk factors. These recurrence patterns and associated risks are highly dependent on the tumor type.

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