- Email: [email protected]
Minimally Invasive Resection of Brain Metastases
Original Article
Minimally Invasive Resection of Brain Metastases Isaac Phang, John Leach, James R.S. Leggate, Konstantina Karabatsou, David Coope, Pietro I. D’Urso
BACKGROUND: Minimally invasive resection of brain metastases aims to maximize resection while minimizing brain trauma.
-
METHODS: Patients with 1 or more metastases that underwent resection following neuro-oncology multidisciplinary meeting discussion from September 2014 to October 2018, with pre- and postoperative magnetic resonance imaging, were included. All patients including posterior fossa metastases or multiple metastases were positioned supine. Hair was not shaved. Volumetric postcontrast T1 magnetic resonance imaging was used for incision planning and neuronavigation. The craniotomy site was tailored to tumor depth according to keyhole principles and ranged between 2 and 5 cm. Intraoperative monitoring and awake mapping were carried out in selected cases.
-
RESULTS: Out of 320 consecutive patients with brain metastases, 44 patients were identified as suitable for minimally invasive resection. Nine patients had no postoperative imaging and were excluded. There were 38 metastases in 35 patients. There were 18 cerebellar metastases, 10 frontal, 3 parietal, 3 occipital, 2 temporal, 1 intraventricular, and 1 basal ganglia. Median length of stay was 3 days (range, 1e24). Average tumor volume was 54.7 cm3 (range, 10e240 cm3). Endoscopic assistance was used in 4 patients. Median performance status improved from 2 to 1 (range, preoperative: 0e4; postoperative: 0e2). Median survival was 14.7 months.
-
CONCLUSIONS: Minimally invasive resection of brain metastasis is safe and effective, and in selected cases confers advantages compared with standard techniques.
-
Key words Brain metastasis - Minimally invasive -
Abbreviations and Acronyms MRI: Magnetic resonance imaging Department of Neurosurgery, Salford Royal NHS Foundation Trust, Stott Lane, Salford, United Kingdom
WORLD NEUROSURGERY -: e1-e6, - 2019
INTRODUCTION
M
inimally invasive surgery represents a new frontier in the surgical treatment of brain tumors. The idea of achieving maximal safe resection with minimal tissue trauma is fascinating for surgeons and patients alike. However, there are challenges with access, bimanual handling, and intraoperative visualization1,2 and there can be an initial steep learning curve. Minimally invasive surgery can be conceived as a way to provide individualized treatment by using the armamentarium of the neuro-oncology surgeon to optimize surgical access, maximize resection, and reduce surgical comorbidity depending on the patient and the tumor. Keyhole approaches have been developed in neurosurgery over the past few decades for the treatment of skull base3 and vascular pathology.4 However, minimally invasive techniques are less commonly used in the treatment of brain metastases.5,6 Here, we review our experience in the treatment of brain metastases with minimally invasive approaches. METHODS Patient Population Approval for the study was obtained from the Salford Royal NHS Foundation Trust research and development office. We conducted a retrospective review of electronic records and collected information regarding patient demographics, clinical presentation, diagnostic imaging, systemic disease, complications, and clinical and radiologic follow-up. All patients affected were discussed in the local neuro-oncology multidisciplinary meeting to gather a consensus view on the management of metastatic brain disease. The decision to recommend surgery was based on factors such as patient comorbidity, performance status, extent of metastatic disease, controllable primary disease, and available further oncologic treatment options. Following a recommendation for surgical resection of brain metastasis, patients referred to the senior author at the multidisciplinary meeting for surgery were offered minimally invasive resection of single or multiple brain metastases. A control
To whom correspondence should be addressed: Pietro D’Urso, M.D., F.R.C.S.(SN) [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.06.091 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter Crown Copyright ª 2019 Published by Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
group of consecutive patients who were recommended for surgery and were referred to other neuro-oncology surgeons for surgery with conventional techniques was also identified. Patient Selection Patients selected for minimally invasive procedures had metastases 1 cm away from the cortical surface or tumors whose most superficial diameter presenting to the cortical surface was up to 5 cm diameter. Metastases whose most superficial diameter was more than 5 cm were excluded as the size of the craniotomy was believed to be closer to more conventional techniques. Surgical Technique Volumetric postcontrast T1 magnetic resonance imaging (MRI) images were acquired preoperatively in all cases and used to plan surgical approach, skin incision, and craniotomy. Patients’ hair was not shaved. Neuronavigation with Stealth or Brainlab (Medtronic Limited, Watford, United Kingdom or Munich, Germany, respectively) was used. All metastatectomies were carried out in supine position, including patients with posterior fossa metastases and cases of multiple metastatectomy. The location and size of skin incision and craniotomy were tailored to the depth of tumor from the cortical surface, its dominant axis, and its volume, according to the keyhole principles2 and ranged between 2 and 5 cm in diameter, depending on the depth of the tumor from cortical
Figure 1. Illustrative cases of minimally invasive resection for brain metastases. (A and B) Axial postcontrast T1 magnetic resonance imaging (MRI) showing right cerebellar metastasis and left premotor metastasis, respectively. (C and D) Bone-windowed radiotherapy planning computed tomography (CT) showing craniotomy size for right cerebellar and left premotor metastastectomy. White arrows show the craniotomies for the
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surface. The approach was tailored to expose only the cortical presenting surface of the tumor, if superficial, minimize approach-related brain trauma to major white matter tracts and navigate along the long axis of the tumor. Natural and dynamic retraction were used. For posterior fossa metastasis, the patient was positioned supine, with the head turned 45 contralaterally to the side of the tumor and 20 neck flexion. Neuronavigation was used to plan a suboccipital skin incision depending on the location and size of the tumor. The procedure was then continued with microsurgical technique and endoscopic assistance as required. The surgeon was usually sitting throughout the procedure to be in line with the main axis of the tumor. An illustrative case in Figure 1 shows a case in which a right cerebellar and a left premotor metastases were resected in 1 operation with intraoperative monitoring. The left premotor metastasis was subtotally resected due to positive stimulation of the corticospinal tract at 8 mA. A detailed discussion of minimally invasive approach for each tumor is beyond the scope of this article. Intraoperative ultrasound was used as an adjunct in all cases. Intraoperative neurophysiology techniques and awake mapping were also carried out in selected cases. Outcome Measures Electronic patient records and imaging were retrospectively reviewed to collect clinical, radiologic, follow-up, and outcome
respective metastases, which were tailored according to keyhole principles. (E and F) Postoperative axial postcontrast T1 MRI showing complete resection of right cerebellar metastasis and subtotal resection of left premotor metastasis. (G) A 5.7 cm metastasis in the right basal ganglia region in another patient. (H) Bone-windowed radiotherapy planning CT showing craniotomy size measuring 4.8 cm.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.091
ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
Table 1. Demographics of Study Population Included Characteristics Sex Male
Excluded
n 10
Control
N (%)
P
Median (range)
8
n ¼ 35
n¼9
n ¼ 35
6
18 (51.4%)
5 (55.6%)
22 (62.9%)
4
62 (29e77)
60 (41e74)
65 (31e83)
Age
2 0
Primary malignancy Breast
6
Colon
4
Endometrial
1
Gastric
1
Lung
14
4
11
Melanoma
5
4
6
Esophageal
2
4
4
Ovarian
1
3
2
Renal
1
1
0
1
1
20
25
Length of stay of control population
6
2
0
10
20
30 40 Number of days
50
60
Figure 2. Length of stay of study and control population.
0
16
One metastasis
33
7
19
Two or more metastases
2
2
16
Intracranial metastatic disease
Adjuvant Treatment Postoperative adjuvant radiotherapy, either fractionated or whole brain, or stereotactic radiosurgery, was offered on an individual basis depending on extent of resection, volume of residual disease, and performance status.
24.7 (14e35) 26.5 (22e30) 25.8 (18e38) 0.16
Length of stay (days)
Mean
10 15 Number of days
8
13
Median (range)
5
n 10
4
Extracranial metastatic disease
Mean body mass index (range)
0
3
Testicular
Number
Length of stay of study population
3 (1e24)
5.5 (3e18)
4 (2e58)
5.2
6.6
9.1
0.04
Statistics The 2-tailed Student t test was used to compare means in Microsoft Excel 2010 (Microsoft Corporation, Redmond, Washington, USA). Significance was taken to be P <0.05. RESULTS
data. Primary outcome measures were extent of resection, postoperative World Health Organization performance status, overall survival, craniotomy diameter versus tumor diameter, and surgical complications. Inpatient and outpatient medical records were reviewed to determine duration of follow-up. Manual segmentation of tumor on Stealth or Brainlab was performed on pre- and postoperative volumetric postcontrast T1 MRI to determine tumor volume. Craniotomy size was measured on radiotherapy planning computed tomography or T1 MRI scans. Patients without postoperative imaging were excluded. Complete resection was defined as no contrast-enhancing disease, near total resection defined as >90% of contrast-enhancing disease resected, and subtotal resection defined as 51%e90% of contrast-enhancing disease resected.
WORLD NEUROSURGERY -: e1-e6, - 2019
Patient Population From September 2014 to October 2018, 320 consecutive patients with brain metastases undergoing surgery were identified. Of these, 44 patients underwent minimally invasive resection of brain metastases. Nine patients had no postoperative imaging and were excluded, leaving 35 patients for analysis. The demographics of all 44 patients who met the inclusion criteria are listed in Table 1. The median length of stay was 3 days (Figure 2). Tumor and Operative Characteristics A total of 38 metastases were resected in 35 patients. One patient had removal of 3 out of 4 metastases in 2 stages, and 1 patient had concomitant removal of 2 out of 4 metastases. Eight patients with multiple metastases had a single metastasis excised. The
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
Table 2. Operative Characteristics of Study Population Study Population
Excluded Population
Characteristics
Control Population
N (%) n ¼ 38
Location of resected metastasis
n¼9
P n ¼ 35
Cerebellar
18 (47.3%)
6 (17.1%)
Frontal
10 (26.3%)
6 (66.7%)
12 (34.2%)
Parietal
3 (7.9%)
2 (22.2%)
6 (17.1%)
Occipital
3 (7.9%)
1 (11.1%)
Temporal
2 (5.3%)
Basal ganglia
1 (2.6%)
Intraventricular
1 (2.6%)
3 (8.6%) 8 (22.9%)
Number of intracranial metastases resected 1
33
2
1
9
35
3
1
53.6 mL (5.2e137.4)
42.7 mL (12.1e78.2)
0.22
29.6 mm (19.4e48.0)
47.1 mm (26.1e78.6)
<0.001
36.8 mm (18.8e56.8)
39.2 mm (17.6e69.2)
0.27
0.8
1.2
Tumor volume Mean (range)
54.8 mL (10e240.0)
Craniotomy diameter (mm) Mean (range) Tumor diameter (mm) Mean (range) Craniotomy:tumor diameter ratio
Performance status
Study group
0
Preop
1 2 3 4
Postop Control group
remaining 25 patients had a solitary metastasis that was excised (Table 1). The operative and postoperative characteristics are listed in Table 2. Endoscopic assistance was required in 4 patients. In 5 patients, the resection was carried out with intraoperative neurophysiology monitoring. Of these 5 patients, the tumor was located in the right precentral gyrus in 1, the left precentral gyrus in 3, and the left supplementary motor area in 1. Gross total resection was achieved in 4 patients. In the patient who underwent resection of a right precentral gyrus tumor with awake mapping, resection was stopped due to positive arm motor stimulation on the posterior margin of the tumor. Near total resection was achieved in this patient.
Pre op
Post op
0%
20%
40%
60%
80%
100%
Figure 3. Preoperative and postoperative performance status of study and control population.
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Outcome Complete resection was achieved in 33 of 38 metastases, near total in 4 of 38, and subtotal in 1 of 38. This compares to complete resection in 21 of 35 metastases, near total in 5 of 35, and subtotal in 9 of 35 in the control group. Median performance status improved from 2 preoperatively to 1 postoperatively (Figure 3). All patients were performance status 2 or better postoperatively. A total of 17 among 35 patients (48.6%) were alive at the time of the last follow-up. Median survival was 14.7 months (Figure 4). In the remaining 18 (51.4%) patients who had died, 10 died
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.091
ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
patient opted for a radical resection accepting the risk of permanent visual field deficit.
% survival 100
DISCUSSION
80
60
40
20 months
0 0
5
10
15
20
25
Figure 4. Survival of study population.
from disease progression, 1 from pneumonia, and 1 from thrombocytopenia. The cause of death for the remaining 6 patients was not available. Mean craniotomy and tumor diameter were 29.6 mm (range, 19.4e48.0) and 36.8 mm (range, 18.77e56.8), respectively, in the study group. The craniotomy diameter to tumor diameter ratio was 0.8. In our control group, mean craniotomy and tumor diameter was 47.1 mm (range, 26.1e78.6) and 39.2 mm (range, 17.63e69.2), respectively. The craniotomy diameter to tumor diameter ratio was 1.2 in the control group. Adjuvant Treatment The average duration of follow-up was 8 months (range, 1e22 months). Thirty-two patients among 35 had postoperative radiotherapy. Of these, 11 were stereotactic radiosurgery, 15 were whole brain radiotherapy, and 6 were fractionated focal radiotherapy. Surgical Complications There were 2 patients who suffered complications. One patient among 35 (2.9%) patients suffered a surgical site infection at postoperative day 14 and required a wound re-exploration and removal of the bone flap. The patient did not suffer postoperative deficits but required a prolonged hospital stay (24 days) for intravenous antibiotics. One patient among 35 (2.9%) patients developed permanent homonymous hemianopia postoperatively. In this patient, the tumor was localized in the lingual gyrus and preoperative imaging showed infiltration of the sulcal arteries; the
REFERENCES 1. Marcus HJ, Cundy TP, Hughes-Hallett A, Yang GZ, Darzi A, Nandi D. Endoscopic and keyhole endoscope-assisted neurosurgical approaches: a qualitative survey on technical challenges and technological solutions. Br J Neurosurg. 2014;28:606-610. 2. Teo C, Sughrue ME. Principles and Practice of Keyhole Brain Surgery. 1st ed. New York, NY: Thieme Publishers; 2015.
We report the results of our series of 35 patients who underwent minimally invasive resection of brain metastases and demonstrate that minimally invasive surgery for the treatment of brain metastasis was safe and effective in our series. Microscopic techniques were used in all cases and endoscopic assistance was required in 4 patients. We were able to achieve complete resection in 85% of cases in a range of tumor volume and locations. All procedures were started with the intention to achieve complete resection. However, in the presented case there was incomplete resection as the tumor was invading the central sulcus. A rim of tumor was left behind to prevent vascular injuries. In other cases, complete resection was not achieved due to indistinct tumor margins. Our complications rate was 5.8% with a median survival comparable to existing literature.7-10 Performance status improved postoperatively in most cases. Minimally invasive approaches should allow for a shorter length of hospital stay.5 In our case series, the median length of stay of 3 days is short, considering that 47% of the metastases were in the posterior fossa. The use of multiple surgical adjuncts including intraoperative ultrasound, intraoperative monitoring and mapping, and endoscopic assistance enabled us to enhance the effectiveness of these minimally invasive approaches. The concept of minimally invasiveness entails careful planning from the beginning of the operation. None of the patients had any hair shaved. This was to recognize the cosmetic problems involved with hair shaving and was integral to patients’ perception of the concept of minimal invasiveness. The infection rates in our series remain the same as reported in the literature.5 Furthermore, all procedures were carried out in supine position, including tumors in the posterior fossa. Particular care was taken to use gravitational retraction of the brain supplemented with dynamic retraction so that no fixed retraction was used at all. Endoscopic assistance was used when necessary. It is an invaluable adjunct to safely approach these tumors, and to inspect the undersurface of the resection cavity for residual disease.6 It did not however completely replace the operative microscope in our series.11 CONCLUSIONS Minimally invasive resection of brain metastasis is safe and effective. It can be combined with intraoperative neurophysiology techniques for disease in eloquent areas to minimize the risk of postoperative deficits.
3. Wilson DA, Duong H, Teo C, Kelly DF. The supraorbital endoscopic approach for tumors. World Neurosurg. 2014;82:e243-e256. 4. Fischer G, Stadie A, Reisch R, et al. The keyhole concept in aneurysm surgery: results of the past 20 years. Neurosurgery. 2011;68(1 Suppl Operative): 45-51 [discussion: 51]. 5. Plaha P, Livermore LJ, Voets N, Pereira E, Cudlip S. Minimally invasive endoscopic resection
WORLD NEUROSURGERY -: e1-e6, - 2019
of intraparenchymal brain tumors. World Neurosurg. 2014;82:1198-1208. 6. Ma R, Coulter CA, Livermore LJ, Voets NL, Al Awar O, Plaha P. Endoscopy in temporal lobe glioma and metastasis resection: is there a role? World Neurosurg. 2018;117:e238-e251. 7. Gazzeri R, Nalavenkata S, Teo C. Minimally invasive key-hole approach for the surgical treatment of single and multiple brain metastases. Clin Neurol Neurosurg. 2014;123:117-126.
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
8. Baker CM, Glenn CA, Briggs RG, et al. Simultaneous resection of multiple metastatic brain tumors with multiple keyhole craniotomies. World Neurosurg. 2017;106:359-367. 9. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastasis to the brain. N Engl J Med. 1990; 322:494-500.
RESECTION OF BRAIN METASTASES
single cerebral 1470-1476.
metastasis.
Cancer.
1996;78:
11. Hardesty DA, Walker CT, Nakaji P. Minimally invasive endoscopic resection of intraparenchymal brain tumors. World Neurosurg. 2015; 83:479-480.
commercial or financial relationships that could be construed as a potential conflict of interest. Received 3 March 2019; accepted 12 June 2019 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.06.091 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
10. Mintz A, Kestle J, Rathbone MP, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any
1878-8750/$ - see front matter Crown Copyright ª 2019 Published by Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.091
Minimally Invasive Resection of Brain Metastases Isaac Phang, John Leach, James R.S. Leggate, Konstantina Karabatsou, David Coope, Pietro I. D’Urso
BACKGROUND: Minimally invasive resection of brain metastases aims to maximize resection while minimizing brain trauma.
-
METHODS: Patients with 1 or more metastases that underwent resection following neuro-oncology multidisciplinary meeting discussion from September 2014 to October 2018, with pre- and postoperative magnetic resonance imaging, were included. All patients including posterior fossa metastases or multiple metastases were positioned supine. Hair was not shaved. Volumetric postcontrast T1 magnetic resonance imaging was used for incision planning and neuronavigation. The craniotomy site was tailored to tumor depth according to keyhole principles and ranged between 2 and 5 cm. Intraoperative monitoring and awake mapping were carried out in selected cases.
-
RESULTS: Out of 320 consecutive patients with brain metastases, 44 patients were identified as suitable for minimally invasive resection. Nine patients had no postoperative imaging and were excluded. There were 38 metastases in 35 patients. There were 18 cerebellar metastases, 10 frontal, 3 parietal, 3 occipital, 2 temporal, 1 intraventricular, and 1 basal ganglia. Median length of stay was 3 days (range, 1e24). Average tumor volume was 54.7 cm3 (range, 10e240 cm3). Endoscopic assistance was used in 4 patients. Median performance status improved from 2 to 1 (range, preoperative: 0e4; postoperative: 0e2). Median survival was 14.7 months.
-
CONCLUSIONS: Minimally invasive resection of brain metastasis is safe and effective, and in selected cases confers advantages compared with standard techniques.
-
Key words Brain metastasis - Minimally invasive -
Abbreviations and Acronyms MRI: Magnetic resonance imaging Department of Neurosurgery, Salford Royal NHS Foundation Trust, Stott Lane, Salford, United Kingdom
WORLD NEUROSURGERY -: e1-e6, - 2019
INTRODUCTION
M
inimally invasive surgery represents a new frontier in the surgical treatment of brain tumors. The idea of achieving maximal safe resection with minimal tissue trauma is fascinating for surgeons and patients alike. However, there are challenges with access, bimanual handling, and intraoperative visualization1,2 and there can be an initial steep learning curve. Minimally invasive surgery can be conceived as a way to provide individualized treatment by using the armamentarium of the neuro-oncology surgeon to optimize surgical access, maximize resection, and reduce surgical comorbidity depending on the patient and the tumor. Keyhole approaches have been developed in neurosurgery over the past few decades for the treatment of skull base3 and vascular pathology.4 However, minimally invasive techniques are less commonly used in the treatment of brain metastases.5,6 Here, we review our experience in the treatment of brain metastases with minimally invasive approaches. METHODS Patient Population Approval for the study was obtained from the Salford Royal NHS Foundation Trust research and development office. We conducted a retrospective review of electronic records and collected information regarding patient demographics, clinical presentation, diagnostic imaging, systemic disease, complications, and clinical and radiologic follow-up. All patients affected were discussed in the local neuro-oncology multidisciplinary meeting to gather a consensus view on the management of metastatic brain disease. The decision to recommend surgery was based on factors such as patient comorbidity, performance status, extent of metastatic disease, controllable primary disease, and available further oncologic treatment options. Following a recommendation for surgical resection of brain metastasis, patients referred to the senior author at the multidisciplinary meeting for surgery were offered minimally invasive resection of single or multiple brain metastases. A control
To whom correspondence should be addressed: Pietro D’Urso, M.D., F.R.C.S.(SN) [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.06.091 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter Crown Copyright ª 2019 Published by Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
group of consecutive patients who were recommended for surgery and were referred to other neuro-oncology surgeons for surgery with conventional techniques was also identified. Patient Selection Patients selected for minimally invasive procedures had metastases 1 cm away from the cortical surface or tumors whose most superficial diameter presenting to the cortical surface was up to 5 cm diameter. Metastases whose most superficial diameter was more than 5 cm were excluded as the size of the craniotomy was believed to be closer to more conventional techniques. Surgical Technique Volumetric postcontrast T1 magnetic resonance imaging (MRI) images were acquired preoperatively in all cases and used to plan surgical approach, skin incision, and craniotomy. Patients’ hair was not shaved. Neuronavigation with Stealth or Brainlab (Medtronic Limited, Watford, United Kingdom or Munich, Germany, respectively) was used. All metastatectomies were carried out in supine position, including patients with posterior fossa metastases and cases of multiple metastatectomy. The location and size of skin incision and craniotomy were tailored to the depth of tumor from the cortical surface, its dominant axis, and its volume, according to the keyhole principles2 and ranged between 2 and 5 cm in diameter, depending on the depth of the tumor from cortical
Figure 1. Illustrative cases of minimally invasive resection for brain metastases. (A and B) Axial postcontrast T1 magnetic resonance imaging (MRI) showing right cerebellar metastasis and left premotor metastasis, respectively. (C and D) Bone-windowed radiotherapy planning computed tomography (CT) showing craniotomy size for right cerebellar and left premotor metastastectomy. White arrows show the craniotomies for the
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surface. The approach was tailored to expose only the cortical presenting surface of the tumor, if superficial, minimize approach-related brain trauma to major white matter tracts and navigate along the long axis of the tumor. Natural and dynamic retraction were used. For posterior fossa metastasis, the patient was positioned supine, with the head turned 45 contralaterally to the side of the tumor and 20 neck flexion. Neuronavigation was used to plan a suboccipital skin incision depending on the location and size of the tumor. The procedure was then continued with microsurgical technique and endoscopic assistance as required. The surgeon was usually sitting throughout the procedure to be in line with the main axis of the tumor. An illustrative case in Figure 1 shows a case in which a right cerebellar and a left premotor metastases were resected in 1 operation with intraoperative monitoring. The left premotor metastasis was subtotally resected due to positive stimulation of the corticospinal tract at 8 mA. A detailed discussion of minimally invasive approach for each tumor is beyond the scope of this article. Intraoperative ultrasound was used as an adjunct in all cases. Intraoperative neurophysiology techniques and awake mapping were also carried out in selected cases. Outcome Measures Electronic patient records and imaging were retrospectively reviewed to collect clinical, radiologic, follow-up, and outcome
respective metastases, which were tailored according to keyhole principles. (E and F) Postoperative axial postcontrast T1 MRI showing complete resection of right cerebellar metastasis and subtotal resection of left premotor metastasis. (G) A 5.7 cm metastasis in the right basal ganglia region in another patient. (H) Bone-windowed radiotherapy planning CT showing craniotomy size measuring 4.8 cm.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.091
ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
Table 1. Demographics of Study Population Included Characteristics Sex Male
Excluded
n 10
Control
N (%)
P
Median (range)
8
n ¼ 35
n¼9
n ¼ 35
6
18 (51.4%)
5 (55.6%)
22 (62.9%)
4
62 (29e77)
60 (41e74)
65 (31e83)
Age
2 0
Primary malignancy Breast
6
Colon
4
Endometrial
1
Gastric
1
Lung
14
4
11
Melanoma
5
4
6
Esophageal
2
4
4
Ovarian
1
3
2
Renal
1
1
0
1
1
20
25
Length of stay of control population
6
2
0
10
20
30 40 Number of days
50
60
Figure 2. Length of stay of study and control population.
0
16
One metastasis
33
7
19
Two or more metastases
2
2
16
Intracranial metastatic disease
Adjuvant Treatment Postoperative adjuvant radiotherapy, either fractionated or whole brain, or stereotactic radiosurgery, was offered on an individual basis depending on extent of resection, volume of residual disease, and performance status.
24.7 (14e35) 26.5 (22e30) 25.8 (18e38) 0.16
Length of stay (days)
Mean
10 15 Number of days
8
13
Median (range)
5
n 10
4
Extracranial metastatic disease
Mean body mass index (range)
0
3
Testicular
Number
Length of stay of study population
3 (1e24)
5.5 (3e18)
4 (2e58)
5.2
6.6
9.1
0.04
Statistics The 2-tailed Student t test was used to compare means in Microsoft Excel 2010 (Microsoft Corporation, Redmond, Washington, USA). Significance was taken to be P <0.05. RESULTS
data. Primary outcome measures were extent of resection, postoperative World Health Organization performance status, overall survival, craniotomy diameter versus tumor diameter, and surgical complications. Inpatient and outpatient medical records were reviewed to determine duration of follow-up. Manual segmentation of tumor on Stealth or Brainlab was performed on pre- and postoperative volumetric postcontrast T1 MRI to determine tumor volume. Craniotomy size was measured on radiotherapy planning computed tomography or T1 MRI scans. Patients without postoperative imaging were excluded. Complete resection was defined as no contrast-enhancing disease, near total resection defined as >90% of contrast-enhancing disease resected, and subtotal resection defined as 51%e90% of contrast-enhancing disease resected.
WORLD NEUROSURGERY -: e1-e6, - 2019
Patient Population From September 2014 to October 2018, 320 consecutive patients with brain metastases undergoing surgery were identified. Of these, 44 patients underwent minimally invasive resection of brain metastases. Nine patients had no postoperative imaging and were excluded, leaving 35 patients for analysis. The demographics of all 44 patients who met the inclusion criteria are listed in Table 1. The median length of stay was 3 days (Figure 2). Tumor and Operative Characteristics A total of 38 metastases were resected in 35 patients. One patient had removal of 3 out of 4 metastases in 2 stages, and 1 patient had concomitant removal of 2 out of 4 metastases. Eight patients with multiple metastases had a single metastasis excised. The
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
Table 2. Operative Characteristics of Study Population Study Population
Excluded Population
Characteristics
Control Population
N (%) n ¼ 38
Location of resected metastasis
n¼9
P n ¼ 35
Cerebellar
18 (47.3%)
6 (17.1%)
Frontal
10 (26.3%)
6 (66.7%)
12 (34.2%)
Parietal
3 (7.9%)
2 (22.2%)
6 (17.1%)
Occipital
3 (7.9%)
1 (11.1%)
Temporal
2 (5.3%)
Basal ganglia
1 (2.6%)
Intraventricular
1 (2.6%)
3 (8.6%) 8 (22.9%)
Number of intracranial metastases resected 1
33
2
1
9
35
3
1
53.6 mL (5.2e137.4)
42.7 mL (12.1e78.2)
0.22
29.6 mm (19.4e48.0)
47.1 mm (26.1e78.6)
<0.001
36.8 mm (18.8e56.8)
39.2 mm (17.6e69.2)
0.27
0.8
1.2
Tumor volume Mean (range)
54.8 mL (10e240.0)
Craniotomy diameter (mm) Mean (range) Tumor diameter (mm) Mean (range) Craniotomy:tumor diameter ratio
Performance status
Study group
0
Preop
1 2 3 4
Postop Control group
remaining 25 patients had a solitary metastasis that was excised (Table 1). The operative and postoperative characteristics are listed in Table 2. Endoscopic assistance was required in 4 patients. In 5 patients, the resection was carried out with intraoperative neurophysiology monitoring. Of these 5 patients, the tumor was located in the right precentral gyrus in 1, the left precentral gyrus in 3, and the left supplementary motor area in 1. Gross total resection was achieved in 4 patients. In the patient who underwent resection of a right precentral gyrus tumor with awake mapping, resection was stopped due to positive arm motor stimulation on the posterior margin of the tumor. Near total resection was achieved in this patient.
Pre op
Post op
0%
20%
40%
60%
80%
100%
Figure 3. Preoperative and postoperative performance status of study and control population.
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Outcome Complete resection was achieved in 33 of 38 metastases, near total in 4 of 38, and subtotal in 1 of 38. This compares to complete resection in 21 of 35 metastases, near total in 5 of 35, and subtotal in 9 of 35 in the control group. Median performance status improved from 2 preoperatively to 1 postoperatively (Figure 3). All patients were performance status 2 or better postoperatively. A total of 17 among 35 patients (48.6%) were alive at the time of the last follow-up. Median survival was 14.7 months (Figure 4). In the remaining 18 (51.4%) patients who had died, 10 died
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ORIGINAL ARTICLE ISAAC PHANG ET AL.
RESECTION OF BRAIN METASTASES
patient opted for a radical resection accepting the risk of permanent visual field deficit.
% survival 100
DISCUSSION
80
60
40
20 months
0 0
5
10
15
20
25
Figure 4. Survival of study population.
from disease progression, 1 from pneumonia, and 1 from thrombocytopenia. The cause of death for the remaining 6 patients was not available. Mean craniotomy and tumor diameter were 29.6 mm (range, 19.4e48.0) and 36.8 mm (range, 18.77e56.8), respectively, in the study group. The craniotomy diameter to tumor diameter ratio was 0.8. In our control group, mean craniotomy and tumor diameter was 47.1 mm (range, 26.1e78.6) and 39.2 mm (range, 17.63e69.2), respectively. The craniotomy diameter to tumor diameter ratio was 1.2 in the control group. Adjuvant Treatment The average duration of follow-up was 8 months (range, 1e22 months). Thirty-two patients among 35 had postoperative radiotherapy. Of these, 11 were stereotactic radiosurgery, 15 were whole brain radiotherapy, and 6 were fractionated focal radiotherapy. Surgical Complications There were 2 patients who suffered complications. One patient among 35 (2.9%) patients suffered a surgical site infection at postoperative day 14 and required a wound re-exploration and removal of the bone flap. The patient did not suffer postoperative deficits but required a prolonged hospital stay (24 days) for intravenous antibiotics. One patient among 35 (2.9%) patients developed permanent homonymous hemianopia postoperatively. In this patient, the tumor was localized in the lingual gyrus and preoperative imaging showed infiltration of the sulcal arteries; the
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We report the results of our series of 35 patients who underwent minimally invasive resection of brain metastases and demonstrate that minimally invasive surgery for the treatment of brain metastasis was safe and effective in our series. Microscopic techniques were used in all cases and endoscopic assistance was required in 4 patients. We were able to achieve complete resection in 85% of cases in a range of tumor volume and locations. All procedures were started with the intention to achieve complete resection. However, in the presented case there was incomplete resection as the tumor was invading the central sulcus. A rim of tumor was left behind to prevent vascular injuries. In other cases, complete resection was not achieved due to indistinct tumor margins. Our complications rate was 5.8% with a median survival comparable to existing literature.7-10 Performance status improved postoperatively in most cases. Minimally invasive approaches should allow for a shorter length of hospital stay.5 In our case series, the median length of stay of 3 days is short, considering that 47% of the metastases were in the posterior fossa. The use of multiple surgical adjuncts including intraoperative ultrasound, intraoperative monitoring and mapping, and endoscopic assistance enabled us to enhance the effectiveness of these minimally invasive approaches. The concept of minimally invasiveness entails careful planning from the beginning of the operation. None of the patients had any hair shaved. This was to recognize the cosmetic problems involved with hair shaving and was integral to patients’ perception of the concept of minimal invasiveness. The infection rates in our series remain the same as reported in the literature.5 Furthermore, all procedures were carried out in supine position, including tumors in the posterior fossa. Particular care was taken to use gravitational retraction of the brain supplemented with dynamic retraction so that no fixed retraction was used at all. Endoscopic assistance was used when necessary. It is an invaluable adjunct to safely approach these tumors, and to inspect the undersurface of the resection cavity for residual disease.6 It did not however completely replace the operative microscope in our series.11 CONCLUSIONS Minimally invasive resection of brain metastasis is safe and effective. It can be combined with intraoperative neurophysiology techniques for disease in eloquent areas to minimize the risk of postoperative deficits.
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commercial or financial relationships that could be construed as a potential conflict of interest. Received 3 March 2019; accepted 12 June 2019 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.06.091 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
10. Mintz A, Kestle J, Rathbone MP, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any
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