Intrafractional 6D Head Movement With Mask Fixation During Stereotactic Intracranial RT-sessions
Conditions: Brain Metastases, Adult
Sponsor: Medical University Innsbruck

 
 
 
 
CLINICAL TRIAL PROTOCOL 
Intrafractional 6D head movement during stereotactic intracranial 
radiation therapy with thermoplastic mask fixation 
A prospective observational study 
 
 
 
Version: 1.0 
Date: 25.01.2019 
 
 
 
 
Principal Investigator 
Ao.Univ.Prof. Dr. Meinhard Nevinny-Stickel 
Universitätsklinik für Strahlentherapie-Radioonkologie 
Medizinische Universität Innsbruck 
Anichstraße 35 
A-6020 Innsbruck 
Sponsor  
Medical University Innsbruck 
Christoph Probst Platz 1 
Innrain 52 
A - 6020 Innsbruck  
 

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1. Study Summary 
Title 
Intrafractional 6D head movement during stereotactic intracranial 
radiation therapy with thermoplastic mask fixation 
Study Center 
single center 
Department of Therapeutic Radiology and Oncology Innsbruck 
Study Design 
/Methodology 
A prospective observational study 
Objectives 
to investigate intrafractional head motion during stereotactic intracranial 
radiation therapy with non invasive thermoplastic mask fixation with 
repeated X-ray position verification during RT sessions. 
Endpoints 
3D deviation of head position, rotational and translational deviations. 
Development of head deviation with time during single RT sessions  
Number of Subjects 
5 
Eligibility Criteria  
Male and female patients with a single intracranial solid tumour. 
Stereotactic radiation therapy with immobilization by non invasive 
thermoplastic mask. 
Study Interventions 
and Measures 
repeated X-ray position verification during RT sessions 
Statistical 
Methodology 
calculation of 3D deviation from X, Y, Z translational deviation. Descriptive 
statistics of 3D, translational and rotational deviation. Analysis of time 
dependent deviation with Spearman’s correlation. ANOVA Analysis of 
deviations in 2-minute interval groups. 
 
 
 

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2. Introduction 
2.1. Study Rationale 
Invasive head fixation by means of a stereotactic ring for stereotactic intracranial radiation therapy has 
largely been replaced by non invasive thermoplastic mask fixation. While the deviation between RT 
sessions can be minimized using modern image guided radiation therapy, the role of intrafractional 
head movement and its effect on treatment accuracy is still debated. Previous studies have attempted 
to estimate intrafractional deviation by performing position measurements at the beginning and the 
end of RT sessions. However, this method is not accurate enough to map patient motions during a 
treatment session. 
2.2. Background and scientific bases 
In recent years advances in non-invasive patient immobilization as well as in image-guided radiation 
therapy (IGRT) have enabled the use of thermoplastic masks and hypofractionated radiotherapy for 
single brain metastases (1). The use of a rigid, invasive stereotactic head-ring provides reliable and 
precise immobilization for single fraction radiosurgery. The ring is securely mounted to the skull using 
pins or screws, thereby achieving a setup inaccuracy of less than 1 mm (2, 3). However, this method 
suffers from disadvantages such as the need to surgically implant the ring. It also entails the risk of 
bleeding and infection, possibly accompanied by pain and generally by patient discomfort. Ring 
implantation, planning and irradiation have to be performed on the same day, which can put a 
significant burden on clinical and organisational resources. Moreover, this prohibits the use of 
fractionated RT. The use of non-invasive thermoplastic masks together with image guidance can 
minimise these limitations and has currently replaced invasive immobilization. (2, 4) 
Several studies have shown that image guidance makes set-up and repositioning uncertainty with the 
non-invasive mask immobilization comparable to that of invasive stereotactic ring application (2, 3, 5, 
6). Nevertheless, this method may have less intrafractional accuracy due to the non-rigid construction 
and indirect immobilization of the skull. This uncertainty can be caused by patient movements during 
individual radiotherapy sessions. Many studies reported this effect only by means of quantifying pre- 
and postfractional deviations of the patient’s head by either CBCT (cone beam computed tomography) 
or ExacTrac (2, 3, 7, 8). However, real intrafractional movements cannot be mapped by measuring the 
position of the head only at the beginning and the end of treatment since this gives no information on 
possible head movements during the individual irradiation treatments, which last up to 20 minutes 
each. Larger deviations would need to be accounted for by increasing the PTV margins, thereby 
exponentially increasing the irradiated volume. Studies have shown that the risk of complications, such 
as radionecrosis, directly correlates with the size of the irradiated PTV (9, 10).  

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2.3. Study objectives 
The purpose of the present study is to evaluate the precision and reliability of mask fixation of the 
head during the entire duration of stereotactic RT sessions. In order to assess position accuracy not 
only at the beginning and the end of the sessions, we repeatedly map deviations of the head position 
in both translation and rotation, by concomitantly measuring intrafractional movement using the 
ExacTrac 6D X-Ray Positioning System (Brainlab AG, Munich, Germany). From the obtained data we 
evaluate the need to adjust safety margins around the gross tumor volume (GTV) whenever the 
investigated thermoplastic mask is used instead of invasive ring fixation.  
3. Study design and Methods 
3.1. General study design 
This is a prospective observational study investigating patient motion during radiation therapy 
sessions of patients treated with stereotactic radiation therapy. 
3.2. Study population 
5 patients treated with intracranial stereotactic radiation therapy for single primary tumours at the 
Department of Therapeutic Radiology and Oncology Innsbruck. 
3.2.1. Inclusion criteria 
 
Males and females ages ≥ 18 
 
Single intracranial primary tumour or metastasis 
 
conventional or hypofractionated stereotactic radiation therapy 
 
position verification with ExacTrac 6D X-Ray Positioning System 
 
Karnovski performance scale 80 or higher 
3.2.2. Exclusion criteria 
 
Position verification with ExacTrac 6D X-Ray Positioning System not possible if the masks 
frame overlaps the orthogonal KV X-ray images used for position measurement.  
3.3. Study procedures 
3.3.1. Date range of the study 
Enrolment of patients between November 2014 and September 2015 

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3.3.2. Procedures 
To detect intrafractional motion during treatment delivery, the ExacTrac in-room based monitoring 
system (Brainlab AG, Munich, Germany) is used (11, 12). It is employed in this study to repeatedly 
record 3D deviations of the target isocenter for both translation and rotation, during a single RT 
session. 
Following thermoplastic mask molding, contrast-enhanced treatment planning CT is performed. CT 
scans are also used for image registration to reference ExacTrac recordings and CBCT-guided patient 
positioning at the beginning of each treatment session. Calculated 6D shifts are checked and, if 
indicated, translational and rotational deviations from reference positions are computed and 
corrected by adjusting the treatment couch (equipped with the HexaPod evo RT system, Elekta AB, 
Stockholm, Sweden) until translational deviation in each direction are < 1.0 mm and rotational errors 
are < 1.0°.  
The first ExacTrac measurement is taken before treatment start at a rotatable baseplate position of 
0°. This initial ExacTrac recording is used as a reference point for comparison with the subsequent 
intrafractional measurements made during irradiation (N = 3 to 10). Patient positions are not 
corrected during a treatment session.  
ExacTrac measurements are taken simultaneously with arc irradiations (five per RT session) at gantry 
angles of 0°, 90°, 180° or 270° with a tolerance range of +/- 10°. For shaped beam application, 
ExacTrac recordings are taken immediately after each field application (five to eight per fraction). A 
final pair of ExacTrac images at a reset baseplate position of 0° are acquired at the end of each 
treatment session.  
4. Data management 
4.1.1. Data sources 
Patient head position data is extracted from the ExacTrac 6D X-Ray Positioning System. 
4.1.2. Data collection and variable abstraction 
The following parameters are extracted, saved in a database and analysed:  
 
baseplate position [°] 
 
elapsed time since treatment start 
 
 X axis translation 
 
Y axis translation 
 
Z axis translation 

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 
X axis rotation 
 
Y axis rotation  
 
Z axis rotation 
 
3D deviation is calculated from X-, Y- and Z-translation 
4.1.3. Data capture methods and storage 
All data collected is be saved databases using Microsoft Excel and IBM SPSS Statistics. The files are be 
stored encrypted on our department’s file servers. Patient identifiers are stored in a separate file. All 
data and records generated throughout the course of the study are kept confidential. Only the study 
investigators have access to the data. In case of publication of the studies results patients personal 
information will be kept confidential. 
5. Statistical analysis 
Translations in the x (medial-lateral), y (superior-inferior) and z (anterior-posterior) directions as well 
as rotations around the x (transversal), y (longitudinal) and z (sagittal) axes are analysed. The resulting 
3DV is calculated as follows: 
3DV = √x² + y² + z² 
IBM SPSS Statistics 22 (IBM Cooperation, Armonk, NY, USA) is used for statistical analysis To evaluate 
the correlation between the time elapsed since the first measurement in each treatment session and 
the 3DV, Spearman’s rank correlation coefficient is calculated. An analysis of variance (ANOVA) is used 
to analyse this correlation further. A p value of < 0.05 is deemed to be significant. 
6. Ethical considerations 
The study is conducted in accordance with the ethical standards of the 1964 Helsinki Declaration and 
its later amendments.There is no risk involved for the participating patients. All parameters and 
measurements required for the study are routinely collected as part of the treatment. All patient data 
is kept confidential and the rights and welfare of the enrolled patients is not adversely affected. Every 
patient is informed about the analysis of data collected over the course of the treatment. Written 
informed consent for this analysis is obtained. While there is no direct benefit for the patients 
participating in the study, results from the study will help improve treatment for future patients 
treated in our department. Information about the accuracy of treatment and the extent of patient 
motion during treatment sessions is vital in order to determine the necessary safety margins used in 

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treatment planning. If patient motion is found to significantly exceed 1 mm an additional safety margin 
will be implemented.  
7. Literature 
1. 
Verellen D, De Ridder M, Storme G. A (short) history of image-guided radiotherapy. Radiother 
Oncol. 2008;86(1):4-13. 
2. 
Ramakrishna N, Rosca F, Friesen S, et al. A clinical comparison of patient setup and intra-
fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery 
system for intracranial lesions. Radiother Oncol. 2010;95(1):109-115. 
3. 
Lamba M, Breneman JC, Warnick RE. Evaluation of image-guided positioning for frameless 
intracranial radiosurgery. Int J Radiat Oncol Biol Phys. 2009;74(3):913-919. 
4. 
Wurm RE, Erbel S, Schwenkert I, et al. Novalis frameless image-guided noninvasive 
radiosurgery: initial experience. Neurosurgery. 2008;62(5 Suppl):A11-17; discussion A17-18. 
5. 
Gevaert T, Verellen D, Tournel K, et al. Setup accuracy of the Novalis ExacTrac 6DOF system 
for frameless radiosurgery. Int J Radiat Oncol Biol Phys. 2012;82(5):1627-1635. 
6. 
Solberg TD, Medin PM, Mullins J, Li S. Quality assurance of immobilization and target 
localization systems for frameless stereotactic cranial and extracranial hypofractionated 
radiotherapy. Int J Radiat Oncol Biol Phys. 2008;71(1 Suppl):S131-135. 
7. 
Linthout N, Verellen D, Tournel K, Storme G. Six dimensional analysis with daily stereoscopic 
x-ray imaging of intrafraction patient motion in head and neck treatments using five points 
fixation masks. Med Phys. 2006;33(2):504-513. 
8. 
Spadea MF, Tagaste B, Riboldi M, et al. Intra-fraction setup variability: IR optical localization 
vs. X-ray imaging in a hypofractionated patient population. Radiat Oncol. 2011;6:38. 
9. 
Blonigen BJ, Steinmetz RD, Levin L, et al. Irradiated volume as a predictor of brain radionecrosis 
after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010;77(4):996-
1001. 
10. 
Minniti G, Clarke E, Lanzetta G, et al. Stereotactic radiosurgery for brain metastases: analysis 
of outcome and risk of brain radionecrosis. Radiat Oncol. 2011;6:48. 
11. 
van Santvoort J, Wiggenraad R, Bos P. Positioning accuracy in stereotactic radiotherapy using 
a mask system with added vacuum mouth piece and stereoscopic X-ray positioning. Int J Radiat 
Oncol Biol Phys. 2008;72(1):261-267. 
12. 
Jin JY, Yin FF, Tenn SE, Medin PM, Solberg TD. Use of the BrainLAB ExacTrac X-Ray 6D system 
in image-guided radiotherapy. Med Dosim. 2008;33(2):124-134. 

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8. Signatures  
o.Univ.Prof. Dr. Ute Ganswindt  
Medizinische Universität Innsbruck 
Representative of Sponsor 
________________________________________ 
Place, Date, Signature 
Ao.Univ.Prof. Dr. Meinhard Nevinny-Stickel 
Universitätsklinik für Strahlentherapie-
Radioonkologie 
Principle Investigator 
________________________________________ 
Place, Date, Signature