Baseline parameters and demographics
The study included 107 patients with a median age of 61 (range 26 - 83) years at the time of operation. Forty-three patients (40.2%) were male. Primary tumor entities comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal tumor (GIT) (10.3%) and other, rare entities (19.6%). At the time of BM relapse, extracranial metastases were present in 61 (57.0%) patients. Detailed demographic and clinical data are displayed in Table 1.
Table 1: Baseline demographic characteristics and parameters
Parameter
|
No.
|
%
|
Median
|
Range
|
Age at operation
£ 65 years
> 65 years
|
75
32
|
70.1
29.9
|
61
|
26-83
|
Gender
Male
female
|
43
64
|
40.2
59.8
|
|
|
Primary tumor
non-small cell lung cancer
Breast cancer
Melanoma
Gastro-intestinal tumor
Other
|
40
21
14
11
21
|
37.4
19.6
13.1
10.3
19.6
|
|
|
Extracranial disease
Stable
Non-stable
|
46
61
|
43.0
57.0
|
|
|
Symptoms (multiple references possible)
Cerebellar
Cognitive
Hemiparesis
Seizures
Headache
Impaired vision
Aphasia
Others
|
19
11
25
14
22
15
13
18
|
17.8
10.3
23.4
13.1
20.6
14.0
12.1
16.8
|
|
|
Previous treatment and clinical status at time of recurrence
Previous cerebral treatment comprised one or more local and/or systemic therapies including surgery, whole brain radiation therapy (WBRT), focal/partial brain radiation therapy (fRT), stereotactic radiosurgery (sRS) and brachytherapy (BT). The number and detailed information on previous treatment modalities were recorded (Table 2).
Table 2: Pre- and postsurgical treatment, surgery, and complications
Parameter
|
No.
|
%
|
Previous treatment
Resection
Radiotherapy
Whole brain radiotherapy
Partial brain radiotherapy
Stereotactic radiosurgery
Brachytherapy
|
44
30
24
53
8
|
41.1
28.0
22.4
49.5
7.5
|
Number of recurrent BM
1 BM
2–3 BM
≥ 4 BM
|
80
19
8
|
74.8
17.8
7.5
|
Extent of resection
Gross total
Subtotal
|
78
29
|
72.9
27.1
|
Adjuvant local treatment
None
Radiotherapy
Whole brain radiotherapy
Partial brain radiotherapy
Stereotactic radiosurgery
Combination
Postsurgical systemic therapy
|
40
67
5
49
11
2
37
|
37.4
62.6
4.7
45.8
10.3
1.9
34.6
|
Cause of death (n = 73)
Neurological
Systemic
Others
unknown
|
37
12
2
22
|
34.6
11.2
1.9
20.6
|
At the time of resection, 79 (73.8%) patients suffered from BM-related symptoms including vertigo, hemiparesis, cognitive impairment, epilepsy, and headache. The median preoperative Karnofsky performance scale (KPS) was 70 (range 40-100).
Surgical treatment, complications, and adjuvant treatment
At time of surgery 80 (74.8%) patients suffered from a single recurrent BM, 19 patients (17.8%) from oligo- (2-3) BM and eight patients (7.5%) from multiple (≥4) BM. Resection of the target lesion was complete (gross total resection) in 78 (72.9%) patients. Surgery was performed in all patients under general anesthesia with the aid of neuro-navigation, ultrasound, and intra-operative monitoring, if required. Surgery improved the Karnofsky performance scale to a median of 80 (0-100). After resection, adjuvant local treatment was administered in 67 patients (62.6%), comprising WBRT (n=5), fRT (n=49), stereotactic radiosurgery (n=11), or a combination of the latter two (n=2). Medical treatment was initiated or continued in 37 (34.6%) patients (Table 2). Surgery-related complications occurred in 28 patients (26.2%) with two patients dying during the acute phase. Details on postsurgical complications and their grading are displayed in detail in Table 3.
Table 3: Complications stratified according to CTCAE (Common Terminology Criteria of Adverse Events)
Complication
|
CTCAE grade
|
n
|
New neurological deficit
|
2
|
6
|
Wound healing disorder
|
2
|
5
|
Wound healing disorder requiring surgery (revision, external drain)
|
3
|
4
|
CSF disorder requiring surgery
|
3
|
3
|
Postoperative haemorrhage requiring intervention
|
4
|
1
|
Cerebral ischemia
|
4
|
1
|
Cerebral edema
|
4
|
1
|
Pulmonary embolism
|
3
|
2
|
Carotic artery dissection
|
4
|
1
|
Pneumonia, sepsis
|
3
|
2
|
Postoperative death
|
5
|
2
|
Survival
In 51 patients (47.7%), a cerebral treatment failure was detected, resulting in a median EFS of 7.1 (95%CI 5.8-8.2) months. None of the factors analyzed influenced EFS.
At the time of analysis, 73 (68.2%) patients had died. Median OS time was 11.1 (95%CI 8.4-13.6) months. Three patients (2.8%) died within the first 30 days after surgery, two from surgical complications. In the remaining cohort, the causes of death were systemic disease progression in 12 patients (11.2%), cerebral progression in 37 patients (34.6%) and other causes in two patients (1.9%). In the remaining patients, the cause of death was unspecified.
In univariate analysis, a pre- and postoperative KPS >70 (p=0.002 and p<0.001) and neurological symptoms caused by BM (p=0.036) were prognostic for survival, while all other parameters (age, primary, number of BM, location, previous treatment, application and type of local treatment, ongoing systemic treatment, extracranial status) showed no significant impact. In multivariate analysis only the postoperative clinical status (HR 0.207 95%CI 0.0816-0.3436; p<0.001) remained independent.