Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome

Abstract

Objective
Occurrence of brain metastases BM is associated with poor prognosis in patients with breast cancer (BC). Magnetic resonance imaging (MRI) is the standard of care in the diagnosis of BM and determines further treatment strategy. The aim of the present study was to evaluate the association between the radiographic markers of BCBM on MRI with other patients’ characteristics and overall survival (OS).

Methods
We included 88 female patients who underwent BCBM surgery in our institution from 2008 to 2019. Data on demographic, clinical, and histopathological characteristics of the patients and postoperative survival were collected from the electronic health records. Radiographic features of BM were assessed upon the preoperative MRI. Univariable and multivariable analyses were performed.

Results
The median OS was 17 months. Of all evaluated radiographic markers of BCBM, only the presence of necrosis was independently associated with OS (14.5 vs 22.5 months, p = 0.027). In turn, intra-tumoral necrosis was more often in individuals with shorter time interval between BC and BM diagnosis (< 3 years, p = 0.035) and preoperative leukocytosis (p = 0.022). Moreover, dural affection of BM was more common in individuals with positive human epidermal growth factor receptor 2 status (p = 0.015) and supratentorial BM location (p = 0.024).

Conclusion
Intra-tumoral necrosis demonstrated significant association with OS after BM surgery in patients with BC. The radiographic pattern of BM on the preoperative MRI depends on certain tumor and clinical characteristics of patients.

Full text

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Acta Neurochirurgica (2022) 164:439–449
https://doi.org/10.1007/s00701-021-05026-4
ORIGINAL ARTICLE - BRAIN TUMORS
Radiographic markers ofbreast cancer brain metastases: relation
toclinical characteristics andpostoperative outcome
AnnaMichel1 · ThiemoDinger1· MarvinDarkwahOppong1· LaurèlRauschenbach1,2· CorneliusDeuschl3·
YahyaAhmadipour1· DanielaPierscianek1· KarstenWrede1· JörgHense4· ChristophPöttgen5·
AntonellaIannaccone6· RainerKimmig6· UlrichSure1· RamazanJabbarli1
Received: 6 August 2021 / Accepted: 9 October 2021 / Published online: 22 October 2021
© The Author(s) 2021, corrected publication 2022
Abstract
Objective Occurrence of brain metastases BM is associated with poor prognosis in patients with breast cancer (BC). Mag-
netic resonance imaging (MRI) is the standard of care in the diagnosis of BM and determines further treatment strategy.
The aim of the present study was to evaluate the association between the radiographic markers of BCBM on MRI with other
patients’ characteristics and overall survival (OS).
Methods We included 88 female patients who underwent BCBM surgery in our institution from 2008 to 2019. Data on
demographic, clinical, and histopathological characteristics of the patients and postoperative survival were collected from
the electronic health records. Radiographic features of BM were assessed upon the preoperative MRI. Univariable and
multivariable analyses were performed.
Results The median OS was 17months. Of all evaluated radiographic markers of BCBM, only the presence of necrosis
was independently associated with OS (14.5 vs 22.5months, p = 0.027). In turn, intra-tumoral necrosis was more often in
individuals with shorter time interval between BC and BM diagnosis (< 3years, p = 0.035) and preoperative leukocytosis
(p = 0.022). Moreover, dural affection of BM was more common in individuals with positive human epidermal growth factor
receptor 2 status (p = 0.015) and supratentorial BM location (p = 0.024).
Conclusion Intra-tumoral necrosis demonstrated significant association with OS after BM surgery in patients with BC.
The radiographic pattern of BM on the preoperative MRI depends on certain tumor and clinical characteristics of patients.
Keywords Breast cancer· Brain metastases· MRI necrosis· HER2
Introduction
The breast cancer [8] is one of the most frequent primary
cancer entities in women with high impact of interest and
prognostic value [6, 9, 53, 68]. Therapy concepts of BC
impacting the patients’ survival include the surgical and
(neo-) adjuvant treatment, the conventional chemotherapy,
endocrine therapy, and radiation, as well as targeted therapy
[18, 25, 34, 43, 46, 55, 56, 69, 72].
Depending on different risk factors and applied treatment,
15–50% of BC patients develop brain metastases [5, 10, 23,
35, 38]. The receptor status (RS) plays an important role for
therapy concepts and the prognosis of breast cancer brain
metastases (BCBM) patients [40, 49, 51, 53, 56]. Individu-
als with triple negative BC and positive status of human
epidermal growth factor receptor 2 (HER2) are prone to BM
[35, 38, 51]. The overall survival (OS) after BM surgery
This article is part of the Topical Collection on Brain Tumors
* Anna Michel
anna.michel@uk-essen.de
1 Department ofNeurosurgery andSpine Surgery, University
Hospital Essen, University Duisburg-Essen, Hufelandstraße
55, 45147Essen, Germany
2 DKFZ Division Translational Neurooncology attheWest
German Cancer Center (WTZ), DKTK Partner Site,
University Hospital Essen, Essen, Germany
3 Department ofRadiology, University Hospital Essen, Essen,
Germany
4 Department ofMedical Oncology, University Hospital Essen,
Essen, Germany
5 Department ofRadiotherapy, University Hospital Essen,
Essen, Germany
6 Department ofObstetrics andGynecology, University
Hospital Essen, Essen, Germany
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depends on multiple factors like Karnofsky Performance
Status (KPS) scale score, number of BM, presence of extrac-
ranial metastases, patients’ age, timing between BC and BM,
histopathological parameters, and (neo-) adjuvant treatments
[3, 11, 20, 31, 33, 35, 60, 61]. In case of BCBM, the median
OS varies between 7.2 and 37.7months. [29, 33, 60]
Magnetic resonance imaging (MRI) is a sensitive diag-
nostic tool and increases the detection rate of BM [10, 26,
38, 57]. Moreover, MRI is commonly used to plan treatment
and to control the cancer disease [2, 22, 36, 39, 50, 52, 65].
Recent studies showed that radiographic markers might have
additional clinical value for the prognostication of postop-
erative survival in patients with lung and breast cancer [1, 7,
8, 12, 13, 15, 24, 45]. As to BCBM, the contrast-enhanced
T1-weighted MRI features were identified as prognostic fac-
tors for therapeutic response after Gamma Knife radiosur-
gery [73]. In this context, the patient and tumor characteris-
tics associated with the radiographic pattern of BM on MRI
are also of clinical relevance. In particular, leptomeningeal
infiltration of BM was more common in individuals with
HER2-positive and triple-negative BC. [28, 30, 41]
To address the clinical value of radiographic markers of
BCBM, we analyzed the association between various radio-
graphic characteristics of BM on the preoperative MRI with
demographic, clinical, and immunohistochemical features
of BCBM patients selected for surgery. A special attention
was drawn on the potential prognostic value of radiographic
markers of BCBM for OS.
Material andmethods
This study was performed in accordance with the Declara-
tion of Helsinki and approved by the local ethics committee
of the University Hospital Essen (local registration number:
17–7855-BO).
Patient population
All female patients (age ≥ 18years) who underwent BM sur-
gery in our institution from January 2008 to December 2019
were included. The cases with missing preoperative MRI
were excluded (n = 9). Treatment strategy and allocation to
BCBM surgery was discussed in the institutional interdisci-
plinary tumor conference. Common criteria for BM surgery
were the size and the mass effect from the lesion(s), presence
of considerable perifocal edema and/or neurological symp-
toms, non-eloquent location, and the KPS score.
Data management
For the evaluation of the radiographic parameters of
BCBM, the T1-, T2-, and contrast-enhanced-weighted
images of the preoperative MRI scans were reviewed by
the first author (A.M., blinded at this time to all clini-
cal, histological, and survival data) for the presence of
following radiographic characteristics of BM: number
(single vs multiple), size (maximal diameter), and loca-
tion (supratentorial vs infratentorial) of BM; intra-tumoral
hemorrhage; contrast enhancement (CE) configuration;
cystic components; necrosis; edema; midline shift; dural
affection; and the relation to the ventricles.
Then, certain clinical and histological features of
BCBM patients were recorded from the electronic health
records: age (at BC and BM diagnosis), the type of BC
surgery (mastectomy vs breast-preserving surgery (BPS)),
trastuzumab therapy of BC, the time interval between the
diagnosis of BC and BM, preoperative KPS scale, extrac-
ranial metastases, RS of BM and BC (hormone recep-
tors: estrogen (ER), progesterone (PR), and HER2), and
the receptor conversion (RC) in BM, as well as OS upon
the available follow-up data. Moreover, two laboratory
parameters at admission were also included for further
correlations as commonly evaluated laboratory markers
for disease progression and survival in BC patients: white
blood cells [16, 27, 44, 47] and lactate dehydrogenase [37,
49, 67]
Statistical analysis
Data were analyzed using SPSS (version 27, SPSS Inc.,
IBM, Chicago, IL, USA) statistical software. The variables
were reported in median values and interquartile ranges
(IQR) between 25 and 75%, or as number of cases (with
percentage), as appropriate. The significance level for the p
value was set at ≤ 0.05. Continuous data were dichotomized
according to the established criteria or using the associa-
tions in the receiver operating characteristic (ROC) curves.
In particular, WBC > 10 × 109/L was referred as leukocytosis
and LDH as pathologically increased. The patients’ age was
dichotomized at 65years. In line with the previous studies
[59], the size of peri-tumoral edema in the preoperative MRI
scans was dichotomized at 10mm.
First, the associations between preoperative MRI charac-
teristics and patients’ demographic, clinical, immunohisto-
chemical, and laboratory parameters were evaluated in uni-
variate analysis using the chi-square (χ2 test) or Fisher exact
tests. Significant associations from the univariable analysis
were transferred to multivariable binary logistic regression
analysis to control for confounders.
The associations between the radiographic markers and
OS were evaluated in the univariable and multivariable Cox
regression analysis in the same manner. To visualize the sur-
vival differences for major study results, the Kaplan–Meier
survival plots and log-rank test were performed.
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Results
Patient population
The final cohort consisted of 88 female patients. The
median OS after BM surgery was 17.0 (7.0–34.8) months.
The initial treatment of BC included BPS and trastuzumab
in 44 (50%) and 26 (29.5%) cases, respectively. Adjuvant
radiotherapy was the standard therapy after BCBM resec-
tion. In some cases, system therapy was also adapted.
In our cohort, 77 (87.5%) received postoperative radio-
therapy. Positive HER2 RS in the BM was identified in
36 cases (40.9%). Table1 summarizes the major baseline
demographic, clinical, and histological characteristics of
the patients in the final cohort. On the preoperative MRI
scans, 42 patients (47.7%) showed singular and supraten-
torial BM. The detailed information on the radiographic
features of BCBM is presented in the Fig.1.
Association betweenMRI markers andother
patients’ characteristics
Univariable analysis
Intra-tumoral hemorrhage was more frequent in individu-
als with poor KPS scale (< 80%) at admission (p = 0.040).
Moreover, younger age at BC diagnosis (p = 0.033), BC
therapy with trastuzumab (p = 0.019), infratentorial BM
(p = 0.027), and positive HER2 RS in BM (p = 0.017) were
associated with dural affection in the preoperative MRI.
Circular CE was identified more commonly in older
patients at BC diagnosis (p = 0.001), in patients without
trastuzumab therapy (p = 0.048), and with negative HER2
RS in BC (p = 0.050). Then, negative HER2 (p = 0.017)
and ER (p = 0.001) RS in BM was also associated with
circular CE in BCBM.
Cystic components in BM were detected more often in
BM with negative ER RS (p = 0.001).
BM with necrosis in MRI showed associations with
poorer initial clinical condition (p = 0.053), trastuzumab
therapy for BC (p = 0.046), shorter time interval between
BC and BM (p = 0.009), negative ER RS in BM (p = 0.049),
and higher rate of leukocytosis at admission (p = 0.007).
BCBM patients without extracranial metastases
(p = 0.027), shorter time interval between BC and BM mani-
festation (p = 0.024), and negative ER RS in BM (p = 0.030)
as well as identic HR status in BC and BM (p = 0.047)
showed more often BM with perifocal edema > 10mm.
Finally, none of the patients’ characteristics showed sig-
nificant associations with the relation of BM to the ventri-
cles (see supplementary table1 and 2).
Multivariable analysis
For dural affection, the following associations remained
significant: supratentorial location of (aOR 3.10, 95% CI
1.16–8.27, p = 0.024) and positive HER2 RS in BM (aOR
3.30, 95% CI 1.26–8.62, p = 0.015). Age ≥ 65years at BC
diagnosis (aOR 5.66, 95% CI 1.18–27.14, p = 0.030) and
negative ER RS in BM (aOR 21.84, 95% CI 2.37–201.49,
p = 0.007) were significantly associated with circular CE.
Table 1 Baseline characteristics of BCBM patients
Abbreviations: Nr. number of cases, BC breast cancer, BM brain
metastasis, IQR interquartile ranges 25–75%, OS overall survival, RS
receptor status, HER2 human epidermal growth factor receptor 2, ER
estrogen receptor, PR progesterone receptor, HR hormone receptors
(= ER and PR), RC receptor conversion
Parameter Median (IQR) or Nr. (%)
Clinical parameters
Number of patients 88 (100%)
OS (months) 17.0 (7.0–34.8)
Preoperative KPS ≥ 80% 77 (87.5%)
Age at BC diagnosis (years) 65.0 (45.0–62.0)
Age at BM diagnosis (years) 55.0 (51.0–68.8)
Time interval BC to BM (months) 42.0 (22.0–100.0)
Number of BM
Singular 58 (65.9%)
Multiple 30 (34.1%)
BM location
Supratentorial 55 (62.5%)
Infratentorial 33 (37.5%)
Surgical treatment of BC
 Mastectomy 42 (47.7%)
 Breast-preserving surgery (BPS) 46 (52.3%)
Trastuzumab therapy of BC 26 (29.5%)
Adjuvant radiotherapy of BM 77 (87.5%)
Extracranial metastases 35 (39.8%)
Immunohistochemically parameters
BM HER2 RS
 Positive 36 (40.9%)
 Negative 52 (59.1%)
BM ER RS
 Positive 45 (51.1%)
 Negative 43 (48.9%)
BM PR RS
 Positive 17 (19.3%)
 Negative 71 (80.7%)
HER2 RC
 Identic 69 (78.4%)
 Converted 9 (10.2%)
HR RC
 Identic 39 (44.3%)
 Converted 39 (44.3%)
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Fig. 1 Radiological informa-
tion’s in preoperative MRI.
a Preoperative radiological
parameters of operated BCBM
patients. The following distribu-
tion of radiological charac-
teristics are available: ven-
tricular contact (19/88, 21.6%),
ventricular infiltration (9/88,
10.2%), intraventricular lesion
(2/88, 2.3%), necrosis (50/88,
56.8%), midline shift (16/88,
18.2%), edema > 10mm (71/88,
80.7%), cystic components
(23/88, 26.1%), circular CE
(19/88, 21.6%), dural affection
(47/88, 53.4%), BM diam-
eter > 30mm (44/88, 50.0%),
and hemorrhage (3/88, 3.4%). b
Preoperative MRI scans: b1 and
b2 demonstrate central necrosis
(hash symbol), perifocal edema
is seen in b3 (black arrowhead)
and b4 shows the circular CE
exemplary. Abbreviation: CE,
contrast enhancement; BM,
brain metastases
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Moreover, two baseline parameters remained significant
in the multivariable analysis for the predictors of necrosis
in preoperative MRI: time interval between BC and BM
(< 3years, aOR 3.10, 95% CI 1.08–8.85, p = 0.035) and
preoperative leukocytosis (aOR 3.44, 95% CI 1.19–9.94,
p = 0.022). Finally, negative ER RS in BM (aOR 3.78, 95%
CI 0.99–14.43, p = 0.05) was the only parameter indepen-
dently associated with peri-tumoral edema in the multivari-
able analysis (see Table2).
Association betweenMRI markers andOS
Univariable analysis: Patients with BM necrosis showed
poorer outcome (median OS 14.50 vs 22.50 months,
p = 0.051). Other radiographic parameters showed no sig-
nificant associations with OS (Fig.2). As to the remaining
patient and tumor characteristics, only the positive HER2
RS in BM (median OS 23.5 vs 13.5months, p = 0.017) and
favorable preoperative KPS scale (≥ 80%, median OS 22.00
vs 7.00months, p = 0.001) showed significant associations
with OS (see supplementary table3).
In the final multivariable Cox regression analysis, MRI
necrosis (aHR 1.78, 95% CI 1.07–2.96, p = 0.027), negative
HER2 RS in BM (aHR 1.88, 95% CI 1.10–3.21, p = 0.020),
and poor preoperative KPS scale scores (aHR 3.33, 95%
CI 1.57–7.06, p = 0.002) were confirmed as independent
predictors for poor OS after BCBM surgery (See Table3).
Figure3 visualizes the association between the number of
present independent predictors and patients’ survival at 1,
2, and 3years.
Discussion
Currently, MRI is the standard of care in the diagnosis and
the evaluation of treatment response in patients with BM.
Increasing epidemiologic relevance of BC in the developed
countries and considerable survival differences necessitate
the identification of simple and reliable prognostic mark-
ers for BC patients which might help to predict the disease
course at its early stage. In this retrospective study, we evalu-
ated the prognostic value of easily assessable radiological
markers of BCBM and found that the necrosis in the preop-
erative MRI scan is independently associated with postop-
erative survival in BCBM patients.
It is generally accepted that patients’ age, BC subtype,
preoperative KPS scale scores, and the presence of extrac-
ranial metastases influence the treatment decisions and
survival in individuals with BCBM [3, 11, 31–33, 35, 42,
51, 60]. The location and the number of BM are also rel-
evant parameters for treatment decision and prognosis. So,
infratentorial BM were associated with higher morbidity and
complications rates in surgical series. [14, 63, 70] Different
risk scores based on the patients’ age, KPS scale values,
and BC subtype, as well as the patterns of intracranial and
extracranial metastases were also confirmed as reliable prog-
nostic markers for BCBM patients [17, 60, 62, 63, 66].
CE MRI is the gold standard in the diagnostics of BM
patients and is crucial for the selection of proper treatment
strategy. Furthermore, different (MRI-based) imaging char-
acteristics of BM were reported as prognostic markers for
survival and treatment response. The radiographic param-
eters which were previously addressed as clinically relevant
markers for cancer patients include the tumor volume; pres-
ence of necrotic, perifocal, and cystic components; peri-focal
edema; and dural affection, as well as the pattern of CE [4,
8, 15, 54, 58, 59, 64, 71, 73].
Several studies demonstrated the impact of CE-weighted
MRIs for the prediction of local tumor control following
Gamma Knife radiosurgery and underlined the correla-
tions between EGFR mutation status and clinical aspects
with radiological features like CE and mass effect of BM in
Table 2 Multivariate analysis of radiological features with clinical,
immunohistochemically, and laboratory parameters
Abbreviations: BC breast cancer, BM brain metastasis, RS receptor
status, HER2 human epidermal growth factor receptor 2, ER estrogen
receptor, HR hormone receptors (= ER and PR (progesterone recep-
tor)), CE contrast enhancement, TI time interval, KPS Karnofsky
Performance status, Preop. preoperative, aOR adjusted odds ratio, CI
confidence interval
Parameter p-value aOR 95% CI
Dural affection
Age at BC diagnosis ≥ 65years 0.097 2.80 0.83–9.41
BM location supratentorial 0.024 3.10 1.16–8.27
BM HER2 RS negative 0.015 3.30 1.26–8.62
Circular CE
Age at BC diagnosis ≥ 65years 0.030 5.66 1.18–27.14
Trastuzumab BC therapy 0.425 2.21 0.32–15.48
BC HER2 RS negative 0.969 1.06 0.06–18.75
BM HER2 RS negative 0.651 1.90 0.12–30.84
BM ER RS negative 0.007 21.84 2.37–201.49
Necrosis
KPS < 90% 0.118 2.35 0.80–6.84
Trastuzumab BC therapy 0.301 1.82 0.58–5.70
TI BC-BM < 3years 0.035 3.10 1.08–8.85
BM ER RS negative 0.268 1.80 0.64–5.08
Preop. WBC (> 10/nL) 0.022 3.44 1.19–9.94
Edema > 10mm
Extracranial metastases 0.108 0.35 0.09–1.26
TI BC-BM < 5years 0.106 2.83 0.80–10.00
BM ER RS negative 0.052 3.78 0.99–14.43
HR RC identic 0.091 3.19 0.83–12.31
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non-small cell lung carcinoma [13, 15, 19, 21]. However,
the data on the clinical value of radiographic BCBM char-
acteristics for the estimation of postoperative survival was
still missing.
In the present study, we have identified heterogeneous
radiological characteristics of BM which can be easily
assessed upon the preoperative MRI imaging without the
application of cost- and time-consuming software solu-
tions. We analyzed the relationship between these simple
radiographic markers with other baseline parameters and OS
of BCBM patients. Of all radiographic BCBM features, only
the presence of intra-tumoral necrosis showed independent
association with postoperative survival in our cohort. Inter-
estingly, BM necrosis was already reported as prognostic
factor for poor local tumor control after Gamma Knife radio-
surgery of lung cancer BM [19, 48].
Although the remaining MRI markers of BCBM showed
no predictive value for OS, but the observed independent
Fig. 2 Prediction for OS in
patients with operated BCBM:
Kaplan Meier curves demon-
strate the radiological param-
eters and their influence on OS.
Only necrosis presents as inde-
pendent prognostic factor for
OS for operated BCBM patients
(necrosis status in preoperative
MRI, log-rank test: p = 0.045).
a BM diameter (log-rank test:
p = 0.285), b cystic components
(log-rank test: p = 0.281), c
dural affection (log-rank test:
p = 0.485), d edema (log-rank
test: p = 0.591), e hemorrhage
(log-rank test: p = 0.792),
f necrosis (log-rank test:
p = 0.045), g ventricular contact
(log-rank test: p = 0.303), and
h circular CE (log-rank test:
p = 0.842). Abbreviations: BM,
brain metastasis; RS, receptor
status; HER2, human epidermal
growth factor receptor 2; KPS,
Karnofsky Performance status;
Preop., preoperative
a BM diameter (log-rank test: p=0.285) bcystic components(log-rank test: p=0.281)
c
dural affection (log-rank test: p=0.485)d edema (log-rank test: p=0.591)
e
hemorrhage (log-rank test: p=0.792) f necrosis (log-rank test: p=0.045)
g
ventricular contact (log-rank test: p=0.303)h circular CE (log-rank test: p=0.842)
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Acta Neurochirurgica (2022) 164:439–449
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associations with other patient and tumor characteristics
might also be of clinical relevance. On one side, BCBM
patients with negative ER RS presented more often with
circular CE and considerable perifocal edema. On another
side, BM with dural affection was more common in HER2-
positive and supratentorial BM. In turn, higher rate of tumor
recurrence was reported for BM with dural contact [64]. In
summary, our findings show that certain histological charac-
teristics (and, possibly, related adjuvant treatment strategies)
might influence the radiographic pattern of BCBM.
Accordingly, the observed association between the
tumor necrosis and OS in our cohort might be related to
certain tumor- and patient-specific characteristics.So,
individuals with shorter time interval between BC and
BM diagnosis showed more often necrotic components
in MRI. Shorter time interval is well established as rel-
evant prognostic factor for BCBM. [20] Another tumor
necrosis-related baseline parameter, the leukocytosis at
admission, was also previously reported as a significant
survival predictor for BC patients [27, 44, 47]. Finally,
the RS and preoperative KPS scale scores which showed
the associations with the necrosis in univariable analy-
sis are acknowledged survival predictors of BC [31, 40,
51, 60]. For the clarification of the biological background
of the association between the tumor features in the MRI
scans with the other patients’ characteristics and postop-
erative survival, further clinical and experimental studies
are mandatory.
Limitations
The retrospective design and the information bias with
regard to non-unique technical features of analyzed preop-
erative MRI scans and partially missing follow-up data are
the major limitations of this monocentric study. Moreover,
imaging interpretation without the use of threshold-based
automated analyses always impairs the risk of investiga-
tor bias. Another limitation of our study is the inability
of assessment of the extent of metastasis resection with
a MRI imaging, since only postoperative computed
tomography scans were routinely performed. However,
according to the surgical reports, complete resection of
BM could be achieved in all cases of the analyzed cohort.
Then, the standard perioperative steroid treatment could
have impacted the development of leukocytosis. However,
the blood sampling and begin of steroid therapy mostly
on the admission day lowers the probability of steroid-
induced leukocytosis in the analyzed patients. Finally,
center-specific selection criteria for BCBM surgery which
might vary between the clinics, particularly, in different
countries, also limit the generalizability of our results.
Therefore, external validation of the analyzed radiographic
markers of BCBM is necessary for the clarification of the
prognostic value of MRI markers for BCBM patients.
Table 3 Multivariate analysis for independent predictors of OS after
BCBM surgery
Abbreviations: aHR adjusted hazard ratio, CI confidence interval, RS
receptor status, BM brain metastases, HER2 human epidermal growth
factor receptor 2, KPS Karnofsky Performance status, preop preop-
erative, MRI magnetic resonance imaging, OS overall survival
Parameter aHR 95% CI p-value
MRI necrosis 1.78 1.07–2.96 0.027
BM HER2 RS negative 1.88 1.10–3.21 0.020
Preop. KPS < 80% 3.33 1.57–7.06 0.002
Fig. 3 Significant survival
predictors in operated BCBM
patients. BM HER2 negative
RS, preoperative KPS < 80%,
and necrosis in preoperative
MRI are predictors for poor
outcome. Prognostic relevant
predictors demonstrate (1year,
2years, 3years) survival rates
[in %] in different subgroups (0,
1, 2, 3 risk factors). Abbrevia-
tions: BM, brain metastases;
HER2, human epidermal
growth factor receptor 2; KPS,
Karnofsky Performance status;
neg, negative; pos, positive
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Acta Neurochirurgica (2022) 164:439–449
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Conclusion
The radiographic pattern of BCBM on the preoperative MRI
depends on certain baseline patient and tumor characteristics
like the RS for ER and HER2, patient’s age, time interval
between BC and BM diagnosis, and preoperative leukocy-
tosis. In turn, tumor necrosis is independently associated
with OS after BCBM surgery. The observed associations
between the radiographic tumor characteristics with other
clinical and immunohistochemical parameters and patients’
survival might be useful for better understanding of tumor
biology in individuals with BCBM.
Supplementary Information The online version contains supplemen-
tary material available at https:// doi. org/ 10. 1007/ s00701- 021- 05026-4.
Author contribution Conceptualization, AM and RJ; methodology,
AM, RJ, and MDO; formal analysis, AM, RJ, and LR; supervision,
RJ; writing (original draft preparation), AM; writing (review and edit-
ing), RJ, MDO, LR, DP, TFD, YA, CD JH, CP, AI, RK, KW, and US.
Funding Open Access funding enabled and organized by Projekt
DEAL.
Declarations
Ethics approval The study was conducted according to the guidelines
of the Declaration of Helsinki and approved by the Ethics Committee of
University Hospital Essen (protocol code: 17–7855-BO, 05.05.2020).
Informed consent Informed consent was obtained from all subjects
involved in the study.
Conflict of interest The authors declare no competing interests.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
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included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article's Creative Commons licence and your intended use is not
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