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Schebesch, K. Brain Metastases. Encyclopedia. Available online: https://encyclopedia.pub/entry/8791 (accessed on 21 January 2026).
Schebesch K. Brain Metastases. Encyclopedia. Available at: https://encyclopedia.pub/entry/8791. Accessed January 21, 2026.
Schebesch, Karl-Michael. "Brain Metastases" Encyclopedia, https://encyclopedia.pub/entry/8791 (accessed January 21, 2026).
Schebesch, K. (2021, April 19). Brain Metastases. In Encyclopedia. https://encyclopedia.pub/entry/8791
Schebesch, Karl-Michael. "Brain Metastases." Encyclopedia. Web. 19 April, 2021.
Brain Metastases
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This entry is adapted from the peer-reviewed paper 10.3390/cancers13071616

Brain Metastases means tumor cell seeding into the central nervous system, mostly localized in the brain parenchyma, the cerebrospinal fluid (CSF), the dura, and the bone structures of the skull, is a frequent complication of advanced cancer. In addition to reduced life span, brain metastases (BM) frequently cause focal neurological deficits, cognitive impairment, and significant life quality reduction.

brain metastases surgical resection infiltration neuronavigation fluorescence-guided surgery

1. Introduction

Cancer is the second most prevalent cause of death worldwide [1], with lung, breast, colorectal, and prostate being the most frequently affected organs [1]. Tumor cell seeding into the central nervous system [2], mostly localized in the brain parenchyma, the cerebrospinal fluid (CSF), the dura, and the bone structures of the skull, is a frequent complication of advanced cancer. In addition to reduced life span, brain metastases (BM) frequently cause focal neurological deficits, cognitive impairment, and significant life quality reduction [3]. By far, outnumbering primary brain tumors by about eight- to ten-fold, BM are the most frequent intraparenchymal tumors of the brain [4] and they show an increasing incidence [5]. There are three potential reasons for this epidemiological trend: (A) the improved imaging technology allows for detecting brain metastases earlier and on a higher frequency in cancer patients [6]. In particular, the high-resolution contrast-enhanced T1-weighted MR imaging in addition to fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging has significantly improved the sensitivity for BM detection [7]; (B) the more effective systemic treatment of systemic cancer, especially the clinical application of first- and second-generation tyrosine kinase inhibitors in addition to immune checkpoint inhibitors, has profoundly increased the life span to the affected patients in which BM can develop [8]; and, (C) the brain shows a restricted bioavailability to several antineoplastic drugs due to the blood-brain barrier (BBB), which is, in contrast to common belief, only heterogeneously altered in BMs [9][10]. Another essential feature of the BBB is the restriction of cellular and humoral immune surveillance leading to a relative immune-privileged status of the brain [11]. This may cause the central nervous system to develop into a refuge site in which metastatic cancer cells are protected from immune–mediated attacks and destruction [12]. Finally, the specific biochemical environment that is regulated by the BBB appears to foster the seeding and proliferation of specific tumor cells, in particular clones with neuroepithelial differentiation, like small cell cancer or melanoma cells [13][14]. The summation of these aspects promotes the development of metastases in the brain as a pharmacological sanctuary compartment, despite successfully controlling the systemic disease [15].

2. Therapies

2.1. The Role of Surgery for Recurrent Brain Metastases

Metastatic tumors of the brain were traditionally considered to be well-delineated with very limited infiltration of the surrounding tissue [16]. Careful histological studies have revised this assumption [17][18], which is corroborated by a significant local recurrence rate after both surgical resection [19] and focal radiotherapy [20]. The improved systemic disease control rates due to modern treatment strategies [8] lead to an increased number of cases with recurrent BM requiring salvage therapy [21]. Surgical re-resection is a valid option in selected patients with recurrent BM, according to a recent review [22]. Unfortunately, there are only retrospective case-series available to establish the beneficial impact of surgery in this setting [22][23][24][25][26][27][28][29][30]. An indication for re-operation was reported in several studies if patients show a rapidly progressing, symptomatic mass lesion that was surgically accessible and at the same time display controlled systemic disease and a good functional condition reflected by a KPI score of >60 [21][27][29][31][32][33]. The median OS after salvage operation ranged between 7.5 months [29] and 20.2 months [21], and depended on presurgical performance status [28], time between initial and salvage BM surgery [24], as well as extent of resection during re-operation [29]. Bindal et al. have summarized all of the potential prognostic factors in a grading system to predict outcome after salvage surgery, including the status of systemic disease, preoperative KPI score, time to recurrence, age, and primary tumor [26]. Consequently, the median survival rates after re-resection of recurrent BM ranged from 13.4 to 3.4 months, depending on the grading score [26]. Interestingly, five retrospective studies reported functional improvement rates in patients with symptomatic BM recurrence between 62–90% after surgical resection [21][24][26][30][32], highlighting the beneficial impact of surgery on symptom burden and functional independency. However, the management of recurrent cerebral metastases is challenging, as the majority has already been treated with radio- and chemotherapy, potentially rendering any cranial re-operation difficult in terms of an increased risk of wound healing disorders, infections, hemorrhages, and CSF-fistulas due to scarring, arachnoiditis, and pathological dural adherences of edematous brain tissue [21][32][34]. The morbidity rates reported in the available studies range from 31% [25] to 0% [21][24][27], and they may depend on the specific status of the patients recruited for the individual studies. Despite the high degree of heterogeneity between the studies, no significantly higher morbidity rate can be concluded between the studies reporting initial [35][19][36][37][38][39] and salvage resection [24][25][26][27][30][31][32] for BM. The same assumption seems to apply to surgical mortality of salvage surgery for BM, which was reported to be between 0% [24][25][26][28][30] and 3.1% [32], and it does not profoundly differ from the mortality rates observed after initial BM resection [35][19][40][41][36][42][38][43]. Taken together, in patients showing a KPI > 60 and a large, symptomatic recurrent metastatic mass, which is surgically accessible, re-resection can provide symptomatic relief and contribute to improved functional independency with acceptable morbidity and mortality rates.

2.2. Local Therapeutic Approaches Alternative to Surgery

Despite the significant development of surgical technology reviewed in this article, the majority of BM patients are not considered to be adequate candidates for microsurgical resection, due to general condition, the level of comorbidities, as well as number and location of the metastatic lesions [8]. Therefore, it is mandatory to mention two alternative local treatment options for BM patients in this context:

2.2.1. Laser Interstitial Thermal Therapy (LITT)

LITT implies the minimally invasive, stereotactically guided application of photons by a fiberoptic laser to eradicate lesions within the brain [44][45]. Most frequently, LITT is used to ablate both primary and secondary brain tumors, radiation necrosis, or epileptic foci [46][47]. The laser induced energy excites intracellular molecules, which leads to thermal energy release and subsequent eradication of the targeted lesion [48]. Pioneered by Sugiyama et al. [49], LITT was not immediately adopted as a neurosurgical technique due to limitations in particular with regard to the precise control of the applied thermal energy resulting in considerable toxicity [50]. However, the development of MRI-based real time thermal imaging has prompted a renaissance of this method [51], with the specific expectation to reduce neurological morbidity and mortality using this approach [52][53]. The current evidence indicates a specific segment of BM patients benefiting the most from LITT: a. Patients presenting with significant comorbidities not allowing for a safe microsurgical removal of the metastatic mass via craniotomy [54] and b. patients who have exhausted radio-oncological options still requiring local therapy due to increasing mass effects [55][56][57]. With regard to the target lesions, there are also several characteristics making LITT a preferrable choice [58]: (a) Deep seated lesions, which are surgically inaccessible. (b) Spherical or oblong configuration without signs of diffuse brain infiltration [45]. (c) Lesions that do not border large vessels or CSF spaces, since these structures may function as a heat sink, preventing the successful application of LITT [46]. In addition, the size of the lesion needs to be taken into account since larger lesions (>60–70 cm3) treated by LITT may be associated with a higher likeliness of clinically relevant LITT-induced cerebral edema [46][57]. In addition, it is mandatory to create complete thermal coverage of the target lesion to achieve maximal tumor control. In one prospective multicenter trial investigating LITT in 42 BM patients, the local recurrence rate was 25% in patients with complete, in contrast to 62.5% after incomplete, ablation [57], indicating that multiple LITT applications may be required under certain circumstances to generate maximal effects [53]. One study comparing surgical resection with LITT in patients with radiation necrosis or tumor recurrence after radiosurgery for BM demonstrated that surgery is superior to LITT in the resolution of neurological symptoms, but it did not cause improved progression free and overall survival rates as compared to LITT [59]. With regard to safety of LITT, the most frequent complications of LITT were intracerebral hemorrhage occurring in 1–14.2% [55][57]; cerebral edema [46][57]; and, neurological deficits both transiently (8.8–35.5%) and permanently (2.2–7.1%) [47][55][57][60]. In conclusion, LITT is a highly useful technology, provided that it is applied to the adequate patient segment, harboring lesions to which LITT is a feasible treatment option.

2.2.2. Stereotactic Radiosurgery (SRS)

Being introduced by Lars Leksell in the 1950s [61], stereotactic radiosurgery is defined as the application of multiple radiation beams focused on a target lesion in a stereotactic setting providing submillimeter precision treatment [62]. Because of its efficacy that is reflected by durable local tumor control rates and low toxicity, SRS has become the standard of care in a segment of patients with BM [63]. When comparing the efficacy of surgical resection versus SRS, the current evidence reflects highly heterogeneous results. Although two trials have demonstrated superior overall survival rates in the patients that were treated with surgical resection [64][65], this was not confirmed by another trial [66]. While two trials failed to detect significant differences in local tumor control rates between groups treated with surgery and SRS [65][67], three other studies reported superior control rates in the SRS treated patients [68][69][70]. Interestingly, one study comparing SRS alone versus the combination of surgical resection and SRS showed the best local control rates in this context [71]. A recent phase III trial attempted to prospectively compare surgery and SRS in BM patients, but it was terminated prematurely due to poor recruitment rates. The results that were derived from the limited number of patients did not show any difference between the local control rates or overall survival [72]. With regard to neurological symptoms, one trial reported superior recovery rates of pre-existing hemiparesis after surgical resection, however also a higher incidence of postsurgical neurological deficits, despite the use of neurophysiological monitoring during resection [73]. In conclusion, BM patients with deep seated, surgically inaccessible and/or multiple lesions are prime candidates for SRS [74]. That applies if the targeted lesions do not require histological or molecular pathologic re-evaluation, do not exceed an axial diameter of 3 cm, and do not cause any obstruction of CSF pathways [75].

3. Conclusions

The surgical resection of a metastatic tumor reduces mass effects and the intracranial pressure, leading to prolonged overall survival. Besides, the decompression of eloquent areas of the brain and normalization of the metabolic microenvironment causes a reduction of symptom burden and improvement of focal neurological deficits, which is associated with intensified adjuvant local and systemic treatment contributing to enhanced survival. Finally, the acquisition of tissue during surgical resection allows for the confirmation of the histological diagnosis of a metastatic tumor and the detection of brain-specific molecular alterations, which may lead to additional therapeutic options in the multimodal treatment of BM patients.

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Subjects: Oncology
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