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O n c o T h e sis
Technical and clinical evaluation of
image guided conformal Arc radiotherapy for localised prostate cancer
Authors
G. Soete (Promotor: Guy Storme, MD, PhD, Department of Radiotherapy, UZ Brussel, Belgium; Date of promotion: May 29th, 2007)
Key words
Prostate cancer, conformal radiotherapy, image guided radiotherapy
Summary
The current thesis summarizes all investigations
leading towards the implementation in daily
routine of image guided conformal Arc therapy
Introduction
Prostate cancer (PC) is currently the most common
male cancer in Flanders. The incidence was 5,354 in
2001, representing 30% of malignant tumours in
men.1 Biochemical control rates for organ confined
prostate cancer after radical prostatectomy, brachytherapy and external beam radiotherapy (RT)
are comparable.2
The purpose of RT is to sterilize malignant tumours
while avoiding complications caused by radiation injury to the surrounding tissues. When prostate-specific antigen (PSA) was introduced in the late ‘80s,
it became apparent that the majority of patients treated with the low radiation doses (≤70 Gy) used at
that time, experienced a rising post-treatment PSA,
indicating subsequent clinical failure. Since then,
several randomised trials have demonstrated significant improved biochemical control with doses ~78
Gy compared to ≤70 Gy. Delivering these high doses with old RT techniques resulted in a high rate of
severe side effects, especially radiation rectitis. Two
recent technical developments have dramatically increased the precision of radiation dose delivery: conformal and image guided RT. Conformal RT (with
or without beam intensity modulation) aims to model the dose distribution to the shape of the target.
Image guided RT (IGRT) aims to deliver this conformal dose distribution to a precise location within
the patient (Figure 1 on page 115).
The current thesis summarizes work leading towards
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for prostate cancer at the Radiotherapy department of the UZ Brussel.
(BJMO 2007:1;114-6)
the implementation in daily routine of image guided
conformal Arc therapy for PC at the Radiotherapy
department of the UZ Brussel.
Image guided conformal Arc therapy
In conventional RT, a simulation is performed in order to locate the radiation isocentre relative to anatomical structures under fluoroscopy. The lasers in
the simulator room are drawn on the patient’s skin
and aligned with the lasers in the treatment room
targeting the linac isocentre prior to each treatment.
Image guided RT refers to the use of an image
modality for patient positioning (X-rays, CT, ultrasound) instead of skin drawings. The IGRT technique developed at the UZ Brussel uses infrared (IR)
reflecting skin marks as a first step in patient setup.
The markers are attached to the skin with self-adhesive film, their position is marked and the patient is
scanned with the markers in place. The location of
the planning isocentre with regard to the markers is
calculated by the planning software. Prior to each
treatment session, the markers are placed on the patient. Their location is detected by IR cameras and
matched to the planning information. The operator
can then enable the couch to automatically align
the planning isocentre with the linac isocentre. The
next step is the actual image guided procedure. The
hardware consists of a pair of X-ray tubes embedded in the floor pointing at two amorphous silicon
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Figure 1. With conventional RT techniques, simple geometric dose distributions such as the rectangular one shown in
the figure are delivered to the target volume, including the
prostate plus a rim of surrounding normal tissues. Conformal
RT and IGRT allow for a reduction of irradiated healthy tissue
in two distinct ways. Conformal RT indicates that the shape
of the dose is adapted to the shape of the target (yellow line).
Accurate positioning e.g. by means of IGRT allows for a reduction of the safety margins around the target (green line).
detectors mounted to the ceiling at ~40° angles. Prior
to each treatment session, a pair of X-rays is made
immediately following the IR positioning. Two options are available. First, an automatic co-registration
of the X-ray images with a reference image from the
planning CT. The second option is a fusion of radio-opaque implanted markers on the X-ray images
with expected marker positions projected on the Xrays based on information from the planning CT.
A correction is then calculated in order to move the
patient to the correct position.
In dynamic Arc therapy, the leaves of the multileaf collimator move during one coplanar rotation to dynamically adapt the shape of the treatment beam to
the projection of the target for each particular angle. The photon fluence inside the dynamic field is
not modulated. Therefore, the technique can not be
classified as intensity modulated RT (IMRT).
Results
The accuracy of the X-ray positioning system was first
assessed by phantom measurements. The resulting
overall 3-dimensional displacement vector was <1
mm and <0.5 mm for fusion of bony landmarks and
implanted markers respectively.3 In two subsequent
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studies, we investigated the accuracy of the X-ray system with respect to bony landmarks in patients, before and after the introduction of a device capable to
correct for rotational setup errors. Setup errors were
reduced for X-ray compared to conventional positioning, and were even further reduced after correction
for rotations (4, 5). A subsequent study addressed
setup accuracy using implanted markers in a clinical
setting. Implanted markers obviously solve the problem of interfraction organ motion. In addition, the
accuracy of marker co-registration was shown to be
superior to bony landmark co-registration. The problem of intrafraction prostate motion is not solved
by the current system.6 Conformal Arc therapy was
compared to five different IMRT solutions by means
of a planning study. This was done for a convex and a
concave target, corresponding to the clinical situation
of “prostate only” versus “prostate plus seminal vesicle
irradiation”. Conformal Arc therapy did not allow for
adequate rectal sparing in case of a concave target but
was equivalent to IMRT for a convex target. Because
of its superior treatment efficiency and hence shorter
treatment time, we consider conformal Arc therapy
the treatment of choice in case of a convex target.7
After implementation of X-ray positioning and
conformal Arc therapy, the clinical results with
respect to side effects and biochemical control appear favourable.8
Conclusion and future prospects
The X-ray image guided positioning system is an integrated system allowing for fast and daily use. The
accuracy of X-ray positioning is superior to the conventional procedure and allows a reduction of safety
margins around the target and hence a smaller volume
of irradiated normal tissue. It was shown that, in patients with a convex target shape, rectal sparing can
be achieved by conformal Arc therapy as effectively as
by IMRT. This fast treatment technique is currently
used in the majority of patients. After implementation of these new techniques, patients experience a
high rate of uncomplicated cure. Our results contribute to the debate whether patients with localized
prostate cancer should be subjected to the hazards
of radical prostatectomy. With modern radiotherapy
techniques, a randomised trial comparing both treatment modalities no longer seems unethical.
In 2005, the UZ Brussel invested in technology to
perform daily CT-based patient positioning, which
could overcome the need for implanted markers. The
positioning and prostate delineation accuracy of this
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Key messages for clinical practice
1. Several randomised trials have demonstrated that prostate cancer patients treated with RT
benefit from high (~78 Gy) compared to conventional radiation doses (≤70 Gy).
2. Using these high dose levels, biochemical control rates for organ confined PC after radical
prostatectomy, brachytherapy and external beam RT are comparable.
3. Two recent technical developments have dramatically increased the precision of radiation dose
delivery and allow for safe administration of these high doses: conformal and image guided RT.
4. Conformal RT refers to modeling the dose distribution to the shape of the target.
5. Image guided RT aims for accurate spatial delivery of this conformal dose distribution within
the patient.
system needs to be evaluated. The system will enable
us to study prostate motion in relation to rectal and
bladder filling. Magnetic resonance imaging (MRI)
was implemented in RT planning for cranial targets
years ago but has only occasionally been used for PC
patients to date. Co-registration software for CT-MRI
in the pelvic region needs to be evaluated. In contrast
to the RT planning CT, MRI allows for visualization
of gross tumour volume in some patients, better delineation of the prostate apex and visualization of the
penile bulb. Whether dose escalation depending on
the macroscopic tumoural lesion determined on MRI,
dynamic contrast enhanced MRI or MRI-spectroscopy is feasible requires further investigation, as well
as the feasibility of penile bulb sparing with possible
positive impact on post-RT erectile function.
References
1. Van Eycken E. Cancer Incidence and Survival in Flanders 20002001. Flemish Cancer Registry Network. Brussels. VLK. 2006.
2. Kupelian PA, Potters L, Khuntia D, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam
radiotherapy ≥72 Gy, permanent seed implantation or combined seeds/external beam radiotherapy for stage T1-T2
prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:25-33.
3. Verellen D, Soete G, Linthout N, Van Acker S, De Roover P,
Vinh-Hung V, Van de Steene J, Storme G. Quality assurance
of a system for improved target localization and patient setup that combines real-time infrared tracking and stereoscopic X-ray imaging. Radiother Oncol 2003;67:129-141.
4. Soete G, Verellen D, Michielsen D, Vinh-Hung V, Van de
Steene J, Van den Berge D, De Roover P, Keuppens F, Storme
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G. Clinical use of stereoscopic X-ray positioning of patients
treated with conformal radiotherapy for prostate cancer.
Int J Radiat Oncol Biol Phys 2002;54:948-952.
5. Soete G, Verellen D, Tournel K, Storme G. Setup accuracy of
stereoscopic X-ray positioning with automated correction for
rotational errors in patients treated with conformal Arc radiotherapy for prostate cancer. Radiother Oncol 2006;80:371-373.
6. Soete G, De Cock M, Verellen D, Michielsen D, Keuppens F,
Storme G. X-ray assisted positioning of patients treated by
conformal Arc radiotherapy for prostate cancer: comparison of setup accuracy using implanted markers versus bony
structures. Int J Radiat Oncol Biol Phys 2007;67:823-827.
7. Verellen D, Linthout N, Soete G, Van Acker S, De Roover P,
Storme G. Considerations on treatment efficiency of different conformal radiation therapy techniques for prostate
cancer. Radiother Oncol 2002;63:27-36.
8. Soete G, Verellen D, Michielsen D, Rappe B, Keuppen F,
Storme G. Image-guided conformation Arc therapy for prostate cancer: Early side effects. Int J Radiat Oncol Biol Phys
2006;66:S141-144.
Correspondence address
G. Soete, MD, PhD
UZ Brussel, Department of Radiotherapy
Laarbeeklaan 101
B-1090 Brussels
Belgium
Phone: 32 2 477 61 44
Fax: 32 2 477 62 12
E-mail: [email protected]
Conflicts of interest: None reported.
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