Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases
Aim : Recent technologic advances have led to the development of frameless radiosurgery. We report our initial results using frameless image-guided radiosurgery for the management of brain metastases. Methods: Over a 2-year period, 16 patients harboring 28 lesions were treated in our institution. 12...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Zitieren: | Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases / Z. Liepa, K. Auslands, D. Apskalne, R. Ozols // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 125-128. — Бібліогр.: 18 назв. — англ. |
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irk-123456789-1386892018-06-20T03:07:26Z Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases Liepa, Z. Auslands, K. Apskalne, D. Ozols, R. Original contributions Aim : Recent technologic advances have led to the development of frameless radiosurgery. We report our initial results using frameless image-guided radiosurgery for the management of brain metastases. Methods: Over a 2-year period, 16 patients harboring 28 lesions were treated in our institution. 12 of 16 patients were treated in a single fraction, but 4 patients were treated using fractioned stereotactic radiotherapy in 3–5 fractions. The maximum target diameter, as determined by T1 — weighted contrast — enhanced magnetic resonance imaging were < 4 cm in all patients. 8 patients (50%) received WBRT (3 Gy in 10 fractions to a total dose of 30 Gy) prior to stereotactic radiosurgery, and were treated with SRS for either lesion progression or new lesions. The total treatment volume for each patient was the sum of the treatment volumes for all treated metastases. The median total treatment volume was 18.63 cm3 (range 1,85–47.03 cm3). Results: Median overall survival time of entire group were 10 months (95% confidence interval 7.470–12.530 months). Of the 3 (11.11%) lesions that showed complete response, all were associated with breast cancer. Partial response was seen in 8 (29.62%) cases. Stable disease was seen in 13 (48.14%) cases, but 3 (11.11%) cases showed progression of disease. Conclusion: Further studies are needed to to match the treatment results with other available modalities to optimize and individualize care of patients with brain metastases. 2012 Article Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases / Z. Liepa, K. Auslands, D. Apskalne, R. Ozols // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 125-128. — Бібліогр.: 18 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/138689 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Liepa, Z. Auslands, K. Apskalne, D. Ozols, R. Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases Experimental Oncology |
| description |
Aim : Recent technologic advances have led to the development of frameless radiosurgery. We report our initial results using frameless image-guided radiosurgery for the management of brain metastases. Methods: Over a 2-year period, 16 patients harboring 28 lesions were treated in our institution. 12 of 16 patients were treated in a single fraction, but 4 patients were treated using fractioned stereotactic radiotherapy in 3–5 fractions. The maximum target diameter, as determined by T1 — weighted contrast — enhanced magnetic resonance imaging were < 4 cm in all patients. 8 patients (50%) received WBRT (3 Gy in 10 fractions to a total dose of 30 Gy) prior to stereotactic radiosurgery, and were treated with SRS for either lesion progression or new lesions. The total treatment volume for each patient was the sum of the treatment volumes for all treated metastases. The median total treatment volume was 18.63 cm3 (range 1,85–47.03 cm3). Results: Median overall survival time of entire group were 10 months (95% confidence interval 7.470–12.530 months). Of the 3 (11.11%) lesions that showed complete response, all were associated with breast cancer. Partial response was seen in 8 (29.62%) cases. Stable disease was seen in 13 (48.14%) cases, but 3 (11.11%) cases showed progression of disease. Conclusion: Further studies are needed to to match the treatment results with other available modalities to optimize and individualize care of patients with brain metastases. |
| format |
Article |
| author |
Liepa, Z. Auslands, K. Apskalne, D. Ozols, R. |
| author_facet |
Liepa, Z. Auslands, K. Apskalne, D. Ozols, R. |
| author_sort |
Liepa, Z. |
| title |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| title_short |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| title_full |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| title_fullStr |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| title_full_unstemmed |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| title_sort |
initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2012 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/138689 |
| citation_txt |
Initial experience with using frameless image-guided radiosurgery for the treatment of brain metastases / Z. Liepa, K. Auslands, D. Apskalne, R. Ozols // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 125-128. — Бібліогр.: 18 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT liepaz initialexperiencewithusingframelessimageguidedradiosurgeryforthetreatmentofbrainmetastases AT auslandsk initialexperiencewithusingframelessimageguidedradiosurgeryforthetreatmentofbrainmetastases AT apskalned initialexperiencewithusingframelessimageguidedradiosurgeryforthetreatmentofbrainmetastases AT ozolsr initialexperiencewithusingframelessimageguidedradiosurgeryforthetreatmentofbrainmetastases |
| first_indexed |
2025-07-10T06:22:16Z |
| last_indexed |
2025-07-10T06:22:16Z |
| _version_ |
1837239938884567040 |
| fulltext |
Experimental Oncology ��� �������� ���� ���ne���� �������� ���� ���ne� ���ne� ���
INITIAL EXPERIENCE WITH USING FRAMELESS IMAGE-GUIDED
RADIOSURGERY FOR THE TREATMENT OF BRAIN METASTASES
Z. Liepa, K. Auslands*, D. Apskalne, R. Ozols
Riga East Clinical University Hospital, Riga LV-1038, Latvia
Aim: Recent technologic advances have led to the development of frameless radiosurgery. We report our initial results using frame-
less image-guided radiosurgery for the management of brain metastases. Methods: Over a 2-year period, 16 patients harboring
28 lesions were treated in our institution. 12 of 16 patients were treated in a single fraction, but 4 patients were treated using
fractioned stereotactic radiotherapy in 3–5 fractions. The maximum target diameter, as determined by T1 — weighted contrast —
enhanced magnetic resonance imaging were < 4 cm in all patients. 8 patients (50%) received WBRT (3 Gy in 10 fractions to a to-
tal dose of 30 Gy) prior to stereotactic radiosurgery, and were treated with SRS for either lesion progression or new lesions. The
total treatment volume for each patient was the sum of the treatment volumes for all treated metastases. The median total treatment
volume was 18.63 cm3 (range 1,85–47.03 cm3). Results: Median overall survival time of entire group were 10 months (95% con-
fidence interval 7.470–12.530 months). Of the 3 (11.11%) lesions that showed complete response, all were associated with breast
cancer. Partial response was seen in 8 (29.62%) cases. Stable disease was seen in 13 (48.14%) cases, but 3 (11.11%) cases showed
progression of disease. Conclusion: Further studies are needed to to match the treatment results with other available modalities
to optimize and individualize care of patients with brain metastases.
Key Words: brain metastases, frameless image-guided radiosurgery.
Brain metastases represent an important ca�se
of morbidity and mortality and may occ�r in �����%
of patients with cancer [�]. The incidence of brain
metastases has increased over time as a conseq�ence
of the increase in overall s�rvival for many types
of cancer and the improved detection by magnetic
resonance imaging �MRI�.
C�rrent treatment options for brain metastases
incl�de s�rgical resection� stereotactic radios�rgery�
whole brain radiation therapy �WBRT�� hypofractio
nated stereotactic radiotherapy� and more recently
chemotherapy aģents with some degree of central
nervo�s system activity [�� �].
In the last �� years radios�rgery in addition to s�r
gery and wholebrain radiotherapy� by virt�e of its
noninvasive nat�re and high lesion control rates� has
emerged as one of key options for patients with brain
metastases [�].
Radios�rgery has been demonstrated to res�lt
in s�perior local control compared with WBRT alone.
Framebased methods of radios�rgery �sing either
LINAC or gamma �nit devices are well established.
Frameless image g�idance as applied to radio
s�rgery describes a method whereby highresol�tion
imaging is obtained at the time of treatment for patient
positioning p�rposes and implies that patient immobi
lization is not obtained with rigid skeletal fixation� b�t
rather with the noninvasive �se of a mask.
Frameless imageg�ided methods in the setting
of singlefraction radios�rgery have as their primary
advantage the potential for improved patient comfort.
As there no sedation or anesthesia is �sed� no vital
monitoring is req�ired. Framebased radios�rgery
methods have a long history� and the reliability of these
methods is not in disp�te. In contrast� since image
g�ided methods are relatively new� few reports are
available detailing clinical res�lts for common applica
tions of this technology.
Since ����� Novalis frameless imageg�ided
radios�rgery �IGRS� system is available in Riga East
Clinical University Hospital and we report o�r initial
res�lts �sing frameless IGRS for the management
of brain metastases.
MATERIAL AND METHODS
The records of patients with brain metastases who
were treated with IGRS in Riga East Clinical Univer
sity Hospital of one or more lesions between �an�ary�
���� and March� ���� were retrospectively reviewed.
Approval of Riga East Clinical University Hospital Medi
cal ethics committee was obtained.
Over a �year period� �6 patients harboring �7 le
sions were treated in o�r instit�tion. Patients were of
fered treatment for metastatic disease of the brain
with one or more metastases and a Karnofsky Perfor
mance Scale score of 7� or greater at time of initial
presentation to o�r clinic. In the patient sample were
represented � male and �� female patients with mean
age �9.�� years �min = ��� max = 7�� SE = ���9��. The
majority �n = �� of patients had brest cancer metas
tases �Table ��. �� patients demonstrated metachro
nos development of metastasis� whereas the others
revealed synchrono�s development. There were
�� cases that presented with one metastasis� � cases
with two metastases� � case with five metastases and
� case with six metastases.
�� of �6 patients were treated in a single fraction�
b�t � patients were treated �sing fractioned stereotactic
radiotherapy in ��� fractions �Table ��. The maxim�m
Received: April 11, 2012.
*Correspondence: E-mail: ka75@inbox.lv
Abbreviations used: fSRT — hypofractionated stereotactic radio-
therapy; IGRS — image-guided radiosurgery; MRI — magnetic res-
onance imaging; SRS — stereotactic radiosurgery; WBRT — whole
brain radiation therapy.
Exp Oncol ����
��� �� �������
��6 Experimental Oncology ��� �������� ���� ���ne�
target diameter� as determined by T�weighted con
trast — enhanced MRI were < � cm in all patients . Eight
patients ���%� received WBRT �� Gy in �� fractions
to a total dose of �� Gy� prior to stereotactic radio
s�rgery� and were treated with SRS for either lesion
progression or new lesions. Other eight patients did not
have WBRT d�ring the st�dy period.
Table 1. Distribution of tumor types in 16 patients
Tumor type Number of patients Number of metastases
breast 8 13
melanoma 2 3
lung 3 7
ovary & cervix 2 3
non-Hodkin’s lymphoma 1 1
Table 2. Treatment modalities used
Treatment mo-
dality
Number
of patients Target (volume range) Marginal dose
(range)
IGRS 9 25.12 cm3 (2.03–47.03) 18 Gy (15–24)
WBRT + IGRS 3 8.15 cm3 (1.85–15.79) 18 Gy (18–20)
WBRT + fSRT 4 22.36 cm3 (6.80–39.47) 15.35Gy
in 3–5 fractions
The treatment isodose vol�me for each metastasis
was calc�lated �sing GammaPlan software. The total
treatment vol�me for each patient was the s�m of the
treatment vol�mes for all treated metastases. The
median total treatment vol�me was ���6� cm� �range
������7.�� cm��.
Patients were followed �p with contrastenhanced
MR imaging at 6�� weeks following SRS treatment
and then every � months �ntil the end period of data
collection or patient demise.
Response criteria to treatment �sed were defined
on the basis of MRI scans as follows: complete re
sponse �CR�� as complete resol�tion of the enhancing
lesion� partial response �PR�� >��% red�ction in the
size of the lesion� stable disease �SD�� no change
in the dimension of the lesion� or < ��% red�ction� and
progression of disease �PD�� > ��% increase in the
size of the lesion.
S�rvival was calc�lated from the date of radios�r
gery to the last follow�p eval�ation or death.
Radiosurgery technique. Patients were immo
bilized d�ring comp�ted tomography �CT� and treat
ments �sing the BrainLAB noninvasiv stereotactic
immobilization mask system.
MRI scan was available for each patient to help
to define the target vol�me. The t�mor was delineated
�sing MRI images and after that coregistration be
tween CT and MRI images was done in order to transfer
target vol�me to CT images that are �sed for dose cal
c�lations. The clinical target vol�me �CTV� was defined
as the �nion of GTVs delineated on MRI images as well
as on CTscans. No margin was added for s�bclinical
extension. The margin for the planning target vol�me
�PTV� was � mm in all directions added to the CTV.
Stereotactic radios�rgery �SRS� was planned with
EclipseTM �Varian Medical Systems INC, USA� treatment
planning system �TPS� �sing vol�metric intensity mod�
lated dose delivery by RapidArcTM �Varian Medical Sys-
tems INC, USA� or intensity mod�lated radiation therapy
�IMRT� with 7�9 intensity mod�lated treatment fields
�Fig. ��. Treatment plan was normalized to ��% isodose
line and normalized ���% isodose line encompassed
the PTV. Linear accelerator NovalisTxTM eq�ipped with
a highdefinition m�ltileaf collimator �MLC ���HD� was
�sed for SRS delivery. All plans were delivered �sing
photon energy 6 MV and dose rate of ���� monitor
�nits �MU� per min�te. For patient position correction�
ExacTrac® 6D �� transversal directions and � rotations�
ImageG�ided Radiotherapy �IGRT� System �BrainLAB
GMBH, Munich, Germany� was �sed.
Fig. 1. CT images with isodose lines showing a treatment plan
of brain metastasis
Quality assurance procedures. All treatment
plans were verified from dosimetric point of view via
complex verification proced�re� which incl�ded dose
plane meas�rements and point dose meas�rements
in phantom and Winston — L�tz test. Dose plane
meas�rements were performed �sing Gafchromic
EBT � films end eval�ated performing gamma index
method. Generally res�lts were considered accept
able if more than 9�% of eval�ated points passed
gamma criteria � mm/�%. Point dose meas�rements
were performed �sing pinpoint �D �PTW, Freiburg,
Germany� ionization chamber. The tolerance level
for the point dose meas�rements was set to �%. The
treatment �nit was considered to be appropriate for
treatment deli very if isocentre sphere� as meas�red
via Winston — L�tz test� did not exceeded � mm.
Statistical methods. S�rvival probability was
estimated with the Kaplan — Meier method. Logrank
test was �sed to test wether there was a difference
between the s�rvival time of different gro�ps of treat
ment. Statistical analysis was performed �sing the
Statistical Package for the Social Sciences �SPSS�.
RESULTS
Median overall s�rvival time of entire gro�p were
�� months �9�% CI 7.�7����.��� months� �Fig. ��.
Overall s�rvival depending on the type of therapy
�p = �.���: WBRT+FSRS �� patients� — median overall
s�rvival were �� months �9�% CI �.������.76� months�;
WBRT+SRS �� patients� — median overall s�rvival were
7 months �9�% confidence interval �.�99���.��� months�;
Experimental Oncology ��� �������� ���� ���ne���� �������� ���� ���ne� ���ne� ��7
SRS �9 patients� — median overall s�rvival were �� months
�9�% confidence interval �.������.��� months�.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Months
Survival function
0 5 10 15 20 25
Months
Overall survival function
Cu
m
ul
at
ive
s
ur
viv
al
1
0.8
0.6
0.4
0.2
0
Fig. 2. Median overall s�rvival time for entire gro�p — �� months
�9�% CI 7��7������ months�
R e g a rd i n g o v e ra l l s � r v i v a l d e p e n d i n g
on the type of t�mor �p = �.�7�: breast cancer �� pa
tients� — ��.�7� months �9�% CI �.�����.7� months�;
l�ng cancer �� patients� — ��.�� months �9�%
CI �����6.�67 months�; melanoma �� patients� —
9 months �9�% CI ����.6� months�.
� ���.��%� patients developed new metastases
following radios�rgery treatment.
Of the � ���.��%� lesions that showed CR� all
were associated with breast cancer. PR was seen
in � ��9.6�%� cases �Fig. �� ��� and were associated
with breast cancer in � cases and � each with ovary�
l�ng and nonHodkin’s lymphoma cancers. SD was
seen in �� ���.��%� cases. These patients incl�ded
� with breast cancer� � with l�ng cancer� � with
melanoma� � with cervix� and � with ovary cancers.
� ���.��%� cases showed PD — � melanoma cancer�
and � l�ng cancer patients.
At the time of data analysis� 9 of the �6 patients
in o�r st�dy gro�p were still alive� 7 had died d�ring
the reporting period.
D�ring follow �p� brain radionecrosis was regis
tered in one patient with melanoma �� month after
SRS. Diagnosis was s�spected by MRI �at the mo
ment SPECT and PET examinations are not available
in Latvia� and confirmed by histological examination
after operation which was done beca�se of s�spected
progression of the disease with mass efect.
Fig. 3. Patient 6�yearold woman with posterior fossa lesion
secondary to metastatic breast cancer
Fig. 4. Follow�p MR image obtained 6 month after treatment
showing s�bstantial red�ction of metastasis vol�me �PR to treat
ment�
DISCUSSION
Brain metastases are a common complica
tion of cancer� with an overall incidence estimated
to be ���� per ��� ��� [�]. Radios�rgery has emerged
as a key method of providing definitive local control for
brain metastases in addition to s�rgery and WBRT [6].
The �se of framebased skeletal immobilization
for stereotactic proced�res has a long history dating
back to the �9��s with the introd�ction of stereotactic
systems designed by Leksell� Talaraich� Reichert and
M�ndinger� Todd and Wells� and others [7].
Stereotactic radios�rgery permits the deli
very of a single high dose of radiation to a target
of ����� cm of maxim�m diameter by �sing gamma
knife �m�ltiple cobalt so�rces� or linear accelerator
�Linac� thro�gh a stereotactic device. The rapid dose
falloff of SRS minimizes the risk of damage to the
s�rro�nding normal nervo�s tiss�e. St�dies have
��� Experimental Oncology ��� �������� ���� ���ne�
demonstrated that the application acc�racy of these
devices is on the order of � mm [�].
In patients with newly diagnosed brain metasta
ses a decrease of symptoms� a local t�mor control
�defined as shrinkage or arrest of growth� at � year
of ���9�% and a median s�rvival of 6��� months have
been reported [9� ��]. Metastases from radioresistant
t�mors� s�ch as melanoma� renal cell carcinoma and
colon cancer� respond to SRS as well as do metastases
from radiosensitive t�mors. Radios�rgery allows the
treatment of brain metastases in almost any location.
The type of radios�rgical proced�re� gammaknife
or Linac based� does not have an impact on the res�lt
[��]. S�rvival following radios�rgery is comparable
with that achieved with s�rgery [9� ��].
The reliable immobilization and target localization
acc�racy of invasive framebased radios�rgery have
established the techniq�e as a gold standart� b�t
it is associated with significant disadvantages. Many
patients consider head frame placement to be a tra�
matic experience. Use of the stereotactic frame does
have some disadvantages incl�ding the proced�ral
discomfort for most patients� with awake placement
being typically performed with local anesthetic only.
Frameplacement involves risk of bleeding and infec
tion� and req�ires premedication. F�rthermore� the
care of patients wearing head frames creates a clinical
reso�rce b�rden on the day of care� req�iring dedi
cated n�rsing and physician s�pport. Framebased
treatment also req�ires treatment planning to be com
pleted following frame placement on the day of treat
ment� making it less feasible to incorporate advanced
dose planning techniq�es s�ch as IMRT. Head frames
may also slip� compromising treatment acc�racy� and
potentially res�lting in inj�ry to the patient [��].
The disadvantages associated with invasive head
frames become of greater concern as more patients
receive radios�rgery� and more are being treated
on m�ltiple occasions. It becomes important to opti
mize patient comfort and treatment efficiency.
The �se of frameless radios�rgery is evolving and
early reports s�ggest similar o�tcomes to patients
treated with framebased radios�rgery [�����]. Also�
high control rates are seen for small lesions in which
spatial precision in dose delivery is critical [�6]. How
ever� the optimal management of brain metastases
remains controversial [�7].
From o�r data d�e to small n�mber of patients
in treatment gro�ps its hard to make definite decisions�
b�t o�r treatment res�lts are compareable to other
available st�dies.
However� s�rgery contin�es to play an essen
tial role in the management of lesions complicated
by mass effect or after fail�re of lessinvasive treat
ment methods [��].
In concl�sion� we present o�r early data and experi
ence to control of brain metastases �sing frameless
IGRS method. F�rther st�dies are needed to match
the treatment res�lts with other available modalities
to optimize and individ�alize care of patients with brain
metastases.
STATEMENT OF CONFLICT OF INTEREST
The a�thors state no conflict of interest.
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