Time-resolved in vivo luminescence dosimetry for online error detection
in pulsed dose-rate brachytherapy
Claus E. Andersena兲
Radiation Research Division, Risø National Laboratory for Sustainable Energy, Technical University
of Denmark, DK-4000 Roskilde, Denmark
Søren Kynde Nielsen
Department of Medical Physics, Aarhus University Hospital, DK-8000 Århus C, Denmark
Jacob Christian Lindegaard
Department of Oncology, Aarhus University Hospital, DK-8000 Århus C, Denmark
Kari Tanderup
Department of Medical Physics, Aarhus University Hospital, DK-8000 Århus C, Denmark
共Received 7 May 2009; revised 17 August 2009; accepted for publication 5 September 2009;
published 6 October 2009兲
Purpose: The purpose of this study is to present and evaluate a dose-verification protocol for
pulsed dose-rate 共PDR兲 brachytherapy based on in vivo time-resolved 共1 s time resolution兲 fibercoupled luminescence dosimetry.
Methods: Five cervix cancer patients undergoing PDR brachytherapy 共Varian GammaMed Plus
with 192Ir兲 were monitored. The treatments comprised from 10 to 50 pulses 共1 pulse/h兲 delivered by
intracavitary/interstitial applicators 共tandem-ring systems and/or needles兲. For each patient, one or
two dosimetry probes were placed directly in or close to the tumor region using stainless steel or
titanium needles. Each dosimeter probe consisted of a small aluminum oxide crystal attached to an
optical fiber cable 共1 mm outer diameter兲 that could guide radioluminescence 共RL兲 and optically
stimulated luminescence 共OSL兲 from the crystal to special readout instrumentation. Positioning
uncertainty and hypothetical dose-delivery errors 共interchanged guide tubes or applicator movements from ⫾5 to ⫾15 mm兲 were simulated in software in order to assess the ability of the system
to detect errors.
Results: For three of the patients, the authors found no significant differences 共P ⬎ 0.01兲 for
comparisons between in vivo measurements and calculated reference values at the level of dose per
dwell position, dose per applicator, or total dose per pulse. The standard deviations of the dose per
pulse were less than 3%, indicating a stable dose delivery and a highly stable geometry of applicators and dosimeter probes during the treatments. For the two other patients, the authors noted
significant deviations for three individual pulses and for one dosimeter probe. These deviations
could have been due to applicator movement during the treatment and one incorrectly positioned
dosimeter probe, respectively. Computer simulations showed that the likelihood of detecting a pair
of interchanged guide tubes increased by a factor of 10 or more for the considered patients when
going from integrating to time-resolved dose verification. The likelihood of detecting a ⫾15 mm
displacement error increased by a factor of 1.5 or more.
Conclusions: In vivo fiber-coupled RL/OSL dosimetry based on detectors placed in standard
brachytherapy needles was demonstrated. The time-resolved dose-rate measurements were found to
provide a good way to visualize the progression and stability of PDR brachytherapy dose delivery,
and time-resolved dose-rate measurements provided an increased sensitivity for detection of dosedelivery errors compared with time-integrated dosimetry. © 2009 American Association of Physicists in Medicine. 关DOI: 10.1118/1.3238102兴
Key words: Al2O3:C, brachytherapy dosimetry, dose verification,
uncertainty
I. INTRODUCTION
A range of quality-assurance 共QA兲 procedures are available
to assure patient safety and high quality of all parts of the
brachytherapy treatment chain 共i.e., everything from device
commissioning to patient-specific treatment procedures兲.1
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Med. Phys. 36 „11…, November 2009
192
Ir, quality assurance,
The objective of dose verification is to test that the planned
dose distribution is actually correctly delivered to the patient.
In vivo dose verification in remotely afterloaded intracavitary
brachytherapy has typically been based on point-detector
measurements in a reference point and/or a critical organ
such as the rectum, bladder, or urethra.2–4 The simple ratio-
0094-2405/2009/36„11…/5033/11/$25.00
© 2009 Am. Assoc. Phys. Med.
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
nale for this approach is that a potential dose-delivery error
would manifest itself 共preferably early in the treatment process兲 in the form of a significant deviation between measurements and plan.
In pulsed dose-rate 共PDR兲 brachytherapy, some of the
main concerns in dose delivery are errors resulting from organ or applicator movements during the treatment, applicator
reconstruction mistakes,5 wrong applicator length, interchanged guide tubes, or afterloader malfunctions. The potential clinical consequences of such errors range from minor to
serious. For remotely afterloaded brachytherapy in general,
the International Commission on Radiological Protection6,7
documented that source positioning errors do happen in the
clinic and that the consequence in some cases has been that
the radiation was delivered outside the prescribed volume
with a complete miss of the target and a risk of side effects
and complications. A Japanese survey of brachytherapy accidents showed that in 224 radiotherapy facilities there were
14 potentially serious brachytherapy events between 2002
and 2004.8
Certain dose-delivery errors 共for example, mechanical obstruction of the source or improperly connected guide tubes兲
can be identified by the afterloader safety systems using, for
example, built-in dummy check sources. Koedooder et al.9
recently analyzed afterloader error log files for 1300 treatment sessions, and concluded that PDR brachytherapy is a
safe treatment modality. Not all errors can, however, presently be detected by the afterloader safety systems. Human
errors such as incorrect connection of applicators to the afterloader 共i.e., interchanged guide tubes兲10 can only be detected on the basis of in vivo dosimetry. As a specific example, Mangold et al.11 reported that in vivo TLD was used
for the identification of a transfer error involving a wrong
needle length specification 共15 cm in stead of 16 cm兲 during
interstitial 192Ir brachytherapy of the breast. Without in vivo
dosimetry, errors leading to overdosage of critical organs
may be discovered at a late stage of the treatment due to
clinical complications for the patient.6 In contrast, errors
leading to underdosage of the target volume will reduce the
change of cure, and such errors may go unnoticed. The practice for using in vivo dosimetry varies considerably among
countries,12 and systematic use of in vivo dosimetry is often
not incorporated as a standard procedure in remotely afterloaded brachytherapy.
Published studies on in vivo brachytherapy dosimetry
have focused on time-integrated dose measurements using
TLDs,4,10,11,13 radiophotoluminescence glass detectors,2
diodes,3,14 or MOSFETs.15,16 In other words, most studies
have been based on the total dose per treatment session
rather than, for example, the dose for individual dwell
positions.
In vivo brachytherapy dosimetry to a large extent translates into knowledge of geometry and the whereabouts of the
source. Nose et al.2 performed in vivo dosimetry in 66 patients with pelvic malignancy undergoing interstitial high
dose-rate 共HDR兲 brachytherapy. Deviations between measurements and calculated doses for the rectum and urethra
were larger than 20% which was found to be attributable to
Medical Physics, Vol. 36, No. 11, November 2009
5034
independent movements of these organs and the applicators.
The ability of in vivo dosimetry to actually detect errors
therefore greatly depends on where the detector probes can
be placed and how well these positions are known. In line
with this, Nakano et al.17 conducted a phantom study that
addressed the feasibility of dose verification directly based
on estimates of HDR brachytherapy source positions derived
from measurements with an array of diamond detectors
placed on the surface of the skin. Time-resolved dosimetry is
needed for the assessment of the dose rate for individual
dwell positions. By time-resolved dosimetry, we mean that
the dose rate at the point of the detector is continuously
recorded second by second during the entire treatment. Tanderup et al.18 demonstrated the application of time-resolved
dosimetry 共in vivo rectal diode dosimetry兲 for assessment of
geometrical stability of applicator and rectum positions during PDR brachytherapy of cervical cancer patients.
In vivo dosimetry may be performed in real time during
remotely afterloaded brachytherapy such that the verification
of measurements against planned dose can be evaluated and
presented online in the brachytherapy control room. This
would enable the possibility of an immediate termination of
treatment in case of significant deviations.17 The relevance of
real-time dose verification seems particularly pronounced for
HDR and PDR brachytherapies since the treatment is typically delivered in a few fractions with a high dose per fraction. Furthermore, PDR brachytherapy typically requires an
overall treatment time of 10–50 h per fraction, and most of
the treatment is therefore carried out automatically without
direct presence of hospital personnel neither in the brachytherapy control room nor with the patient. Online in vivo
dosimetry in brachytherapy can be carried out using, for example, semiconductor detectors15,16,19–22 and fiber-coupled
luminescence detectors based on organic scintillators,23–27
aluminum oxide crystals,28,29 or other materials.30,31 A concern with the fiber-coupled dosimetry systems could be that
optical fiber cables are difficult to handle in a clinical environment since they have a critical bending radius and should
preferably not be subject to pulls or mechanical stress.
The objective of the present work was to present and
evaluate an online dose-verification protocol for PDR
brachytherapy based on time-resolved dosimetry 共1 s time
resolution兲 using one or two point detectors placed close to
or directly in the tumor region using standard brachytherapy
applicator needles. The proposed protocol was evaluated on
the basis of in vivo measurements for cervix cancer patients
undergoing PDR brachytherapy. Furthermore, software
simulations were used in a sensitivity analysis to assess if
certain hypothetical errors would have been detected with
the proposed protocol had they occurred during the actual
treatments.
II. METHODS AND MATERIALS
II.A. Patients
In vivo measurements were undertaken for five cervix
cancer patients undergoing PDR brachytherapy with a Varian
GammaMed Plus afterloader and an 192Ir source 共⬃3.7
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
5035
TABLE I. Patient treatment details and information about the two luminescence probes 共labeled A and B兲. A Martinez universal perineal interstitial template
共MUPID兲 was used for patient 1, and the ring in modified tandem-ring applicators was used as template for needle implantation for patients 3 and 5 共Ref. 32兲.
Luminescence dosimeter probes
Source-to-probe distancea
Patient
Applicators
共active兲
No. of dwell positions
No. of pulses
A
B
A 共mm兲
B 共mm兲
1
2
3
4
5
15 needles
Tandem and ring
Tandem and two needles
Tandem
Tandem and four needles
52
26
8
11
32
50
10
15
15
20
Interstitial needle
None
Intracavitary needle
Intracavitary needle
None
Interstitial needle
Intracavitary needle
In rectum
Intracavitary needle
Interstitial needle
34 共14–58兲
–
32 共9–42兲
29 共13–52兲
–
37 共5–58兲
26 共11–65兲
41 共26–53兲
27 共12–50兲
22 共10–45兲
Dwell-time weighted mean and range 共minimum− maximum兲.
a
⫻ 1010 Bq initial activity兲. The treatments comprised from
10 to 50 pulses 共1 pulse/h兲 delivered by intracavitary/
interstitial applicators 共tandem-ring systems and/or needles兲.
For each patient, one or two luminescence dosimeter probes
共labeled A and B, respectively兲 were placed directly in or
close to the tumor region using rigid needles 共1.3 mm inner
diameter兲 of stainless steel 共patient 1兲 or titanium 共patients
2–5兲. The needles were classified as being either interstitial
or intracavitary needles. The interstitial needles were implanted through soft tissue into the tumor whereas the intracavitary needles were placed in the vagina with the tip anchored in the ring of modified tandem-ring applicators.32 The
interstitial needles were only used for dosimetry in cases
when these remained unloaded after the actual treatment
planning. For one patient, a luminescence dosimeter probe
was placed in a rectal catheter. Additional information is
given in Table I including a summary of the source-to-probe
distances. Figure 1 shows as an example specific details for
patient 1. The positions of all applicators and dosimeters
were reconstructed in the treatment planning system 共TPS兲
共BRACHYVISION 7.5, Varian, Palo Alto, CA兲 on the basis of
CT/MR scans acquired immediately before the treatment.
II.B. Luminescence dosimeter system
Luminescence dosimetry was performed using an optical
method involving single highly sensitive aluminum oxide
crystals 共Al2O3 : C兲 共Ref. 33兲 attached to thin optical fiber
FIG. 1. Patient 1 details. The left picture shows the afterloader with the 192Ir
source and the 15 guide tubes used in the treatment. The two optical fiber
cables for dosimeter probes A and B are guided to separate interstitial stainless steel needles inside the patient. The right picture shows a CT scan of the
patient with applicators. The position of the dosimeter probes 共A and B兲 are
indicated in the picture.
Medical Physics, Vol. 36, No. 11, November 2009
cables 共1 mm outer diameter兲. This instrumentation and its
characteristics for 192Ir dosimetry were recently described
elsewhere.29 The purpose of the 15 m fiber cable was to
guide the light between the dosimeter crystal and the remote
readout instrumentation placed in the brachytherapy control
room. The method uses two luminescence signals. First, socalled radioluminescence 共RL兲 is generated spontaneously in
Al2O3 : C during irradiation. This scintillator-like signal can
be used for time-resolved monitoring of the dose delivery
共1 s time resolution兲.34 Second, the crystal also acts as a
passive dosimeter, and the accumulated dose for a single
treatment pulse can be obtained while the dosimeter is still in
the patient by optical stimulation of the Al2O3 : C crystal.
This optically stimulated luminescence 共OSL兲 signal is the
direct optical equivalent of thermoluminescence.35 Light is
also generated when the fiber cable itself is irradiated, and
this so-called stem signal is a source of error for the RL
measurements as these two signals cannot be discriminated
with the present instrumentation. The OSL is not subject to
this source of error as the readout takes place after the irradiations 共the stem signal is a combination of Cerenkov light
and fluorescence which decay at the time scale of picoseconds兲.
The measurements in the present study were carried out
automatically during the treatments in accordance with the
protocols described in Ref. 29. The alteration between the
two readout modes, RL 共during treatment pulses兲 and OSL
共between treatment pulses兲, was triggered on the basis of an
online analysis of the data. The luminescence dosimetry system was operated independently from the afterloader and the
identification and aggregation of measured doses for individual applicators or dwell positions were based entirely on
the time structure in the treatment plan. Due to imperfections
in this procedure, dwell positions with a real-time duration of
⬍5 s were not included in the dose verification based on
individual dwell positions. The dosimetry system was calibrated using water phantom measurements obtained before
and after the treatments.29 Note that within each session, the
same 192Ir source was used for both calibration and patient
treatments. The stem signal was measured in a water phantom set up with the 192Ir source placed approximately 10 mm
from the fiber cable and 80 mm away from the dosimeter
crystal. The same two reader instruments were used for all
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
five patient measurements, but after patient 1, neutral density
filters were removed from the instruments to make them
more sensitive.
II.C. TPS reference doses
Reference doses were calculated for each patient in accordance with the AAPM-TG43 protocol36,37 as implemented in
our own software programed in S 共S-PLUS, version 7, TIBCO,
Palo Alto, CA兲. These reference values will be referred to as
TPS values. The software also predicts the progression of
dose delivery second by second under consideration for the
order of applicators and dwell positions in the treatment plan
and afterloader transit times between applicators 共⬃20 s兲
and dwell positions 共⬃0 s兲. Correction for decay of the 192Ir
source within each treatment session is not performed.
II.D. Simulated dose-delivery errors „sensitivity
analysis…
Calculations were also made for a range of hypothetical
errors comprising either 共i兲 interchange of pairs of guide
tubes 共one pair per event兲 or 共ii兲 applicator displacement errors of ⫾5, ⫾10, and ⫾15 mm 共one applicator and displacement distance per event兲. Imposing a displacement error of 5
mm 共for example, as a result of a reconstruction mistake or
because of a movement of the applicator during the treatment兲 means that all dwell positions in that applicator will be
offset by 5 mm relative to the original plan coordinates. For
tandems or needles, the offset is modeled to occur along the
principal axis of the applicator. For rings, the offset will result in a simple rotation of all dwell positions by 5 mm
within the ring.
5036
in Ref. 29: Either 5% if the measurements were based on
OSL results or 8% if they were based on RL results. The
absolute contribution of 2 mGy originated from measured
variations in the background counting rates. To illustrate the
relative importance of uM and uTPS as a function of detectorsource distance, we applied the above techniques in a simulation of an 192Ir depth-dose curve in water.
To assess the influence of the stem signal on the RL measurements, we calculated the extent to which the fiber cables
were irradiated for each individual dwell position in the five
treatments. Specifically, we calculated the line integral 共in
units of Gy cm s−1兲 of the dose rate for 8 cm of fiber cable
starting at the end of the crystal. The orientation of the fiber
cables were known from the location of the applicators.
II.F. Test statistics
Given a measured dose 共or dose rate兲 D M for a certain
dwell position, applicator or treatment pulse, and the corresponding TPS reference dose 共or dose rate兲 DTPS, we define
the standardized deviation d between the two values as
d=
D M − DTPS
,
2
冑u2M + uTPS
共1兲
where u M and uTPS are standard uncertainties of measurements and reference values, respectively, as defined in Sec.
II E. In the absence of systematic errors, we expect d to
approximately follow a normal distribution function with
zero mean and unity standard deviation, and we therefore
define a measurement-plan deviation to be significant if
兩d兩 ⬎ 2.58 corresponding to a P level of 0.01.
III. RESULTS
II.E. Uncertainty analysis
III.A. Positioning uncertainty calculations
The software was used for analyzing the impact of position uncertainty on TPS reference doses. It was assumed that
the xyz coordinates of dwell positions and detector positions
each were associated with a standard uncertainty 共i.e., one
standard deviation as defined elsewhere38兲 u p equal to 1 mm.
Error propagation was carried out using a simple Monte
Carlo technique: For each of the six coordinates 共xyz for the
source and xyz for the probe兲, we independently sampled
random values from normal distribution functions with
means equal to the plan values and standard deviations equal
to u p 共i.e., 1 mm for all degrees of freedom兲. This procedure
was repeated 1000 times for all dwell positions and resulted
in distributions of possible TPS doses to the detector for
every dwell position. The results were summed for each of
the 1000 Monte Carlo realizations to give distributions of
doses at the level of each individual applicator and subsequently for each individual patient. Standard deviations uTPS
of these results were calculated for all separate dwell positions, applicators, and patients.
The dose measurements were associated with a standard
uncertainty called u M which was estimated as the quadrature
sum of an absolute contribution of 2 mGy 共or 0.2 mGy/s for
dose-rate results兲 and the relative standard uncertainty found
Figure 2 共top panel兲 shows the calculated basic depthdose curve going from 0.25 Gy at 7 mm to 5 mGy at 50 mm
for a 10 s irradiation time at each depth. The middle panel in
the same figure shows the relative contribution of positioning
uncertainty 共uTPS兲 and measurement uncertainty 共uM 兲 as a
function of source-to-detector distance. It is noted that positioning uncertainty dominates close to the source whereas
the measurement uncertainty dominates at long distances.
The figure shows that the combined uncertainty 共uc兲 of uTPS
and u M has a minimum at about 25 mm source-to-probe distance. The bottom panel shows the displacement needed to
make a significant 共P = 0.01兲 dose-to-plan deviation according to the test statistics described in Sec. II F. The plot shows
that about 3 mm displacements can be detected close to the
source whereas displacements larger than 16 mm are needed
for detection at 50 mm distance.
Medical Physics, Vol. 36, No. 11, November 2009
III.B. Integrated and time-resolved results
Figure 3 shows the dose per pulse for the five patients
using either OSL or RL. Generally, the dose delivery appears
to have been quite stable. However, some differences from
patient to patient should be noted: The results for the inter-
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
Patient 1
Depth dose curve
0.35
0.2 0
[Gy]
0.30
0.15
95% CI
TPS
s = 1.8%
Probe B
OSL
RL
0.50
0.10
0.40
0.05
s = 2.7%
0.30
0.0
0
Uncertainty components
60
60
[%]
Probe A
0.40
0.2 5
uTPS
40
40
20
40
30
50
Probe B
1.6
1.2
uc
s = 7.7%
0.8
0
Detectable displacement
15
15
Dose per pulse [Gy]
uM
0
10
Patient 2
20
20
[mm]
5037
2
4
6
8
Patient 3
Probe A
0.3
0.2
s = 1.6%
0.1
0.0
0.18
10
10
10
Probe B
0.16
s = 4.6%
0.14
5
0
5
10
10
20
20
30
30
40
40
50
50
[mm]
Source-to-probe distance [m
FIG. 2. Illustration of the relationship between uncertainty, ability to detect
source displacements, and source-to-probe distance for a 10 s irradiation
period with an 192Ir source identical to the one used for the treatments. The
top panel shows the basic depth-dose curve going from 0.25 Gy at 7 mm to
5 mGy at 50 mm. The middle panel shows the various uncertainty components used in Eq. 共1兲. The uncertainties are given relative to the dose at the
given depth. uc is the combined uncertainty of uTPS and u M which represent
the 1 mm positioning uncertainty of TPS reference values and the RL measurement uncertainty, respectively. The bottom panel shows the approximate
displacement distances that can be detected.
15
Patient 4
1.8
0
10
Probe A
1.6
1.4
s = 1.3%
Probe B
1.2
2.4
2.0
1.6
s = 0.7%
1.2
0
5
15
10
Patient 5
Probe B
1.2
1.1
1.0
s = 0.5%
0.9
stitial probe in patient 5 were highly stable 共0.5% relative
standard deviation兲 whereas the rectal measurements with
probe B for patient 3 were much more variable 共4.6% relative standard deviation兲 although still random. In contrast,
the measurements for patient 1, probe B included a small
systematic decrease in the dose as the treatment progressed.
For patient 2, we note an abrupt ⬃15% shift after pulse 3.
Figure 3 indicates that there was good agreement between
the RL and OSL results for all five patients which is interesting since the two signals are partly subjected to different
sources of errors.29 The figure also shows that there was
qualitatively good agreement between measurements and
TPS reference values for all cases except patient 3, probe A
where all measurements were significantly lower than the
TPS value. Figure 4 shows the time-resolved dose delivery
during the first treatment pulse for each patient and the corresponding TPS reference profiles. The number of applicators in use for each patient can readily be identified from the
Medical Physics, Vol. 36, No. 11, November 2009
0
5
10
Pulse no.
15
20
FIG. 3. Measurement results for the dose per pulse for the five patients using
either RL 共crosses兲 or OSL 共circles兲. The mean relative standard deviations
共s兲 are given within each panel. Within each panel, the reference TPS dose
is indicated by a horizontal line and a shaded band which shows a 95%
confidence interval calculated from the Monte Carlo simulations of the influence of 1 mm positioning uncertainty on the predicted TPS values.
plots 共cf. Table I兲 as the measured dose rate approaches zero
during an ⬃20 s period when the source changed from one
applicator to the next. Many of the individual dwell positions
can also be identified from the plots due to the change in
dose rate from one position to the next. The plots show that
there was qualitatively good agreement between measurements and TPS reference values for all cases except patient
3, probe A.
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
Patient 1
TPS reference
Measurements
4
3
2
Probe A
Guide tube 1
10
0.362 Gy
0.439 Gy
15
4
Probe B
10
2
5
0
0
Guide tube 4
6
200
1.084 Gy
600
400
Patient 2
Probe B
4
2
Dose rate [mGy/s]
0
3.0
200
0.062 Gy
400
600
Guide tube 5
TPS = 1.00 Gy
Simul. = 1.04 Gy
Diff. = 4.1%
Dose rate [mGy/s]
0
10
8
6
4
2
800
0
Patient 3
15 mm displacement of applicator 3
Probe A
2.0
10
TPS = 1.00 Gy
Simul. = 0.80 Gy
Diff. = -21%
8
1.0
6
0.0
0.8
0.6
0.4
0.2
0.0
TPS = 1.00 Gy
Simul. = 0.74 Gy
Diff. = -27%
6
0
0
Guide tube 3
TPS reference
Simulation
8
1
5038
Probe B
0.145 Gy
4
2
0
0
8
100
1.363 Gy
6
300
200
0
400
Patient 4
Probe A
2
Probe B
1.508 Gy
6
200
300
400
500
Time [s]
4
0
8
100
4
2
FIG. 5. Simulated dose-delivery errors for patient 5, probe B: 共i兲 Guide
tubes 1 and 3 have been interchanged 共top panel兲, 共ii兲 guide tubes 4 and 5
have been interchanged 共middle panel兲, and 共iii兲 applicator 3 has been displaced 15 mm 共bottom panel兲. The thick solid lines are the simulated measurements and the dashed line is the original TPS reference profile. The
integrated doses are given within each panel. The shaded band shows a 95%
confidence interval for the predicted TPS values resulting from the 1 mm
positioning uncertainty.
0
0
8
200
1.077 Gy
6
600
400
800
Patient 5
Probe B
4
2
0
0
100
200
300
400
500
Time [s]
FIG. 4. Time-resolved dose-rate measurements 共thick lines兲 during the first
pulse for the five patients undergoing PDR brachytherapy. The step curve is
the calculated TPS reference dose-rate profile and the shaded blue band is
the associated 95% confidence interval. It is indicated within each panel
whether the measurement results were obtained with dosimeter probe A or
B. The time integral of the measured dose rates is stated within each panel.
for the instruments used for patient 1 and approximately
4500 counts per Gy cm for the instruments used for patients
2–5. By comparison with the actual count rates, it was estimated that one dwell position was estimated to be associated
with as much as 30% of stem signal 共patient 1, probe A兲 and
that nine dwell positions were associated with a stem signal
larger than 10% for either of the two probes. All dwell positions for patient 1 with dwell times larger than 5 s were
estimated to be influenced by less than 5% stem signal. The
influence of the stem signal for individual dwell positions for
patients 2–5 was in all cases less than 3%. The influence of
the stem signal on the integral RL doses was estimated to be
less than 3% for patient 1 共both probes兲 and less than 1% for
the other patients.
III.C. Stem-signal calculations
The integrated fiber cable dose rate 共averaged over the
entire treatment兲 ranged from 0.002 Gy cm s−1 for patient 1,
probe A to less than 0.0001 Gy cm s−1 for patient 4, probe
A. The maximum integrated fiber cable dose rate was calculated for patient 1, probe B, where one dwell position was
estimated to be associated with an irradiation of
0.028 Gy cm s−1. It was found that approximately 1000
counts would be generated per Gy cm fiber cable exposure
Medical Physics, Vol. 36, No. 11, November 2009
III.D. Dose verification
Table II shows the calculated measurement-plan discrepancies for all five patients in accordance with the statistical
test described in Sec. II F. The results are given in the form
of so-called error ratios E / T where E is the number of
measurement-plan comparisons that deviate significantly
共P = 0.01兲 and where T is the number of considered comparisons. For an error-free dose delivery, all E’s should ideally
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
5039
TABLE II. Dose-delivery error ratios E / T for the five patients based on in vivo measurements with probe A or B
and calculated TPS reference values. E is the number of significant deviations 共P = 0.01兲 defined in relation with
Eq. 共1兲 and T is the total number of considered comparisons. The error ratios are broken down by 共i兲 dose for
each patient, 共ii兲 dose for each applicator, and 共iii兲 dose rate for each dwell position. Only positions with dwell
times longer than 5 s are included in group 共iii兲. All error ratios are given on the basis of individual pulses. The
columns “RL” and “OSL” indicate if the measurements were based on radioluminescence or optically stimulated luminescence, respectively. Probe A was not used for patients 2 and 5.
Full pulse
Patient
Probe
RL
OSL
Applicator
RL
Dwell positiona
RL
1
1
2
3
3
4
4
5
A
B
B
A
B
A
B
B
0/50
0/50
0/10
15/15
0/15
0/15
0/15
0/20
0/50
0/50
3/10
15/15
0/15
0/15
0/15
0/20
0/750
0/750
0/20
45/45
3/45
0/15
0/15
0/100
0/1300
0/1300
19/230
60/120
0/120
0/165
0/165
0/540
With dwell times ⬎5 s.
a
be zero. The comparisons are organized hierarchically on the
basis of 共i兲 total dose per pulse, 共ii兲 dose per applicator, and
共iii兲 dose per dwell position. Comparisons are made for each
individual pulse in the treatment, so the total number of applicator comparisons for patient 1, for example, amounts to
750 because there are 50 treatment pulses and 15 applicators.
It can be seen from the table that the measurements for patients 1, 4, and 5 did not significantly deviate from the TPS
reference values at any of the three levels of comparison
共dwell position, applicator, or pulse total兲. In contrast, we
note significant deviations for patient 3, probe A. The results
with probe B for the same patient are, however, generally in
agreement with the TPS reference values 共the only deviations
are for 3 out of 45 comparisons at the level of dose per
individual applicator兲. For patient 2, the main deviation occurs for three of the pulses.
III.E. Detection of simulated error events
Figure 5 shows examples of simulated error events for
patient 5. The examples with interchange of two guide tubes
共either guide tubes 1 and 3 or guide tubes 4 and 5兲 lead to a
marked difference between the TPS reference profile for the
correct treatment and the expected time-resolved measurements. The impact on the integrated dose per pulse is, however, marginal 共4.1%兲 in the example involving guide tubes 4
and 5 and therefore cannot be detected using dose verification without time resolution. The example in the bottom
panel of Fig. 5 with a 15 mm displacement for all dwell
positions in applicator 3 leads to an ⬃20% change in the
integrated dose per pulse and a marked change in the timeresolved measurements.
Tables III and IV summarize all simulated error events for
guide tube interchanges and applicator displacements, respectively. The calculations are based on test statistics described in Sec. II F, and we classify a dose-delivery error
event to be detected if at least one of the considered
measurement-plan comparisons for a given patient deviates
Medical Physics, Vol. 36, No. 11, November 2009
significantly 共P = 0.01 per independent comparison兲. The
comparisons are organized hierarchically on the basis of 共i兲
dose per pulse, 共ii兲 dose per applicator, and 共iii兲 dose per
dwell position. The error-event detection ratio F / S gives the
number of detected error events 共F兲 over the total number of
considered error events 共S兲. An ideal dose-verification system should have a detection ratio of 100%. The number of
considered error events S in the table can be calculated as
follows: For the guide-tube error events, we note, as an example, that the treatment of patient 1 comprised 15 guide
tubes which leads to 105 possible pairs of guide-tube permutations. Likewise, the number of ⫾5 mm applicator displacement errors for this patient amounts to 15⫻ 2 = 30 since only
one applicator is considered per error event. Table III shows
that the ability to detect guide-tube errors increases when we
change the dose verification from integrated to time-resolved
values. For probe A in patient 1, we estimate that only 5 out
of 105 of the considered guide-tube permutations could be
detected if based on time-integrated results whereas this ratios is 72/105 for applicator based dosimetry and 73/105 for
dwell-position dosimetry. Likewise, we estimate that only
1/10 guide-tube error events would be detected for probe B,
TABLE III. Sensitivity for detection of interchanged guide tubes. This table
shows dose-delivery error ratios F / S for the simulated errors where F is the
number of detected errors and S is the number of considered error events.
The error detection ratios are calculated separately for each treatment pulse,
applicator, and dwell position. Patient 4 is not included in the table as this
treatment only included one applicator.
Patient
Probe
Full pulse
Applicator
Dwell position
1
1
2
3
3
5
A
B
B
A
B
B
5/105
7/105
0/1
0/3
0/3
1/10
72/105
70/105
1/1
0/3
0/3
9/10
73/105
70/105
1/1
3/3
3/3
10/10
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
5040
TABLE IV. Sensitivity for detection of applicator displacements of ⫾5, ⫾10, and ⫾15 mm. This table shows dose-delivery error ratios F / S for the simulated
errors where F is the number of detected errors and S is the number of considered error events. The error detection ratios are calculated separately for each
treatment pulse, applicator, and dwell position.
Full pulse
Applicator
Dwell position
Patient
Probe
⫾5 mm
⫾10 mm
⫾15 mm
⫾5 mm
⫾10 mm
⫾15 mm
⫾5 mm
⫾10 mm
⫾15 mm
1
1
2
3
3
4
4
5
A
B
B
A
B
A
B
B
0/30
1/30
1/4
1/6
0/6
0/2
0/2
0/10
0/30
2/30
2/4
2/6
0/6
1/2
1/2
0/10
0/30
2/30
2/4
2/6
1/6
1/2
1/2
0/10
0/30
1/30
2/4
2/6
0/6
0/2
0/2
0/10
3/30
5/30
2/4
6/6
6/6
1/2
1/2
2/10
5/30
5/30
2/4
6/6
6/6
1/2
1/2
6/10
0/30
2/30
1/4
1/6
0/6
1/2
1/2
2/10
0/30
6/30
2/4
6/6
3/6
2/2
2/2
4/10
2/30
6/30
3/4
6/6
6/6
2/2
2/2
9/10
patient 5 if the dose verification is based on time-integrated
values versus 9/10 and 10/10 for the dose verification based
on individual applicators or dwell positions, respectively. A
similar trend is seen in Table IV for the detection of applicator displacement errors. For example, none of the ten cases
involving ⫾15 mm displacements of patient 5 applicators
can be detected using time-integrated dosimetry whereas this
detection ratio increases to 6/10 for the applicator based dosimetry and 9/10 for the dwell-position based dosimetry.
IV. DISCUSSION
IV.A. Feasibility of fiber-coupled RL/OSL in vivo
dosimetry
The study confirms the feasibility of performing in vivo
luminescence radiotherapy dosimetry with aluminum oxide
crystals attached to optical fiber cables as first demonstrated
with in vivo OSL dosimetry for a head-and-neck cancer patient undergoing intensity modulated radiation therapy at
Copenhagen University Hospital, Denmark.39 As expected
from long-term laboratory tests40 and preclinical phantom
measurements,29 the RL/OSL dosimetry system was found to
be suitable for in vivo 192Ir brachytherapy dosimetry from the
perspective of measurement uncertainty and sensitivity. The
overall main feature of the system was the ability of the 1
mm dosimeter probes to fit into standard guide tubes and
applicators. We are not aware of published works that directly present in vivo time-resolved dose verification on the
basis of measurement from standard applicators used in remotely afterloaded brachytherapy.
IV.B. Dose-verification outcome
The concept of dose-verification explored in this work is
based on a direct comparison of in vivo point measurements
and TPS values at the position共s兲 of the dosimeter共s兲. Generally the in vivo measurements agreed well with the calculated TPS reference values as shown in Figs. 3 and 4 and
Table II. The agreement concerned dwell times, dose-rate
patterns, dose per pulse for individual dwell positions, applicators and patients, and the results indicated a stable dose
delivery in most cases. The main measurement-plan discrepMedical Physics, Vol. 36, No. 11, November 2009
ancy was for patient 3, probe A. This deviation is believed to
have been caused by a gross error on the position of the
dosimeter probe. The probe was probably not correctly inserted into its intercavitary needle and the measured dose
rate indicates that the crystal was placed about 35 mm from
the assumed position at the bottom of the needle channel. It
should be pointed out that the other probe for that patient
共probe B兲 gave results in good agreement with the TPS reference values. These measurements were carried out before
the software was able to procedure online measurement-plan
comparisons, so no extra effort was made to clarify the origin of this discrepancy during the actual treatment. Likewise,
the reason for the discrepancy of the initial three pulses for
patient 2, probe B remains unknown. For patients 1, 4, and 5,
no significant measurement-plan deviations were observed
for neither probe A nor probe B.
IV.C. Time-resolved versus integral dose verification
The RL signal provided measurements of the dose delivery with a time resolution of 1 s, and these measurements
could therefore be used to assess the dose for each dwell
position, applicator, or pulse total which in turn could be
compared with the corresponding TPS reference values. The
results in Tables III and IV showed that the estimated ability
to detect error events increased with improvements in time
resolution. For example, we could estimate that less than 5%
of the considered guide-tube errors for patient 1 would be
detected on the basis of integral doses 共for example, as
would be obtained with TLDs兲 whereas the estimated errorevent detection ratio was about 70% with time-resolved dose
verification even at the level of just knowing the dose delivered for each applicator.
The increased ability to detect errors with time-resolved
dose verification is simple: The relative importance of, for
example, a displacement of a given applicator will be larger
if the dose for that particular applicator can be considered in
isolation from other parts of the plan. Likewise for the considered guide-tube errors, the extra integrated dose received
from one applicator could be partly balanced by a similar
decrease in integral dose from another guide tube 共see
middle panel in Fig. 5兲.
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Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
It should be pointed out that the present study addresses
the use of independent point detectors. The above conclusion
in favor of time-resolved dosimetry does not imply that the
best overall dose verification 共i.e., the one that will help identify only the real problems兲 is achieved in this way. The use
of integral dosimetry with, for example, a stack of TLDs
共Ref. 10兲 or a linear array of semiconductors15,16 provides an
improvement in spatial resolution which may be better than
using one or two independent point detectors with time resolution. The study only suggests that on a detector-bydetector basis, time-resolved dose verification is always to be
preferred whenever possible.
It is relatively easy to calculate integral doses for each
pulse and applicator 共due to the long delay between these兲
whereas the dose rate for given dwell positions are more
difficult to extract. The latter problem is caused by the lack
of any communication link between afterloader and doseverification system which on the other hand could be viewed
as an important feature as it would otherwise compromise
the independence of the dose verification.
IV.D. Where to perform the measurements
The particularly good agreement between measurements
and TPS reference values for patients 1 and 5 could suggest
that measurements in interstitial needles are to be preferred
whenever possible. For treatments that anyway involve a
large number of needles and long treatment times 共such as
the 50 h treatment of patient 1兲, it may be justified to insert
one or two additional interstitial needles just for the purpose
of in vivo dosimetry.
The proposed simple formalism for dose verification 共Sec.
II F兲 explicitly requires detailed knowledge of the uncertainties for both TPS reference values 共uTPS兲 and measured doses
or dose rates 共u M 兲. Figure 2 共bottom panel兲 illustrated that
from the perspective of error detection, it is optimal to be as
close to the source as possible. The data in Table I therefore
suggest that probe B for patient 5 was probably the best
placed probe for dose verification as it on the average was
only 22 mm away from the source 共range of 10–45 mm兲
whereas the rectal probe for patient 3 共probe B兲 was in the
worst position as this probe on the average was 41 mm away
共range of 26–53 mm兲. The technique for fixation of the fiber
probes at the bottom of applicator needles could probably be
improved, and in at least one case 共patient 3, probe A as
already discussed兲 it appears that one dosimeter probe was
not correctly positioned within the applicator.
IV.E. Measurement uncertainty
Assuming that the five patients were indeed administered
the correct treatment, then Table II indicates to what degree
the proposed in vivo dose-verification protocol will generate
false alarms. From the selected significance level for error
detection 共P = 0.01兲 we a priori would expect that about 1%
of all comparisons would by random result in significant
measurement-plan deviations. The error ratios in Table II are,
however, generally much lower. For example, none of the
1300 dwell-position comparisons for patient 1, probe A reMedical Physics, Vol. 36, No. 11, November 2009
5041
sulted in significant deviations. The reason for the discrepancy could be that the involved uncertainties are not independent. If, for example, the basic calibration of the detector
system is off by 10% in one comparison, then it will also be
so in the next one. The 1% rate of false alarms is the expected random error rate for any given comparison if repeated many times for different treatment sessions and with a
recalibrated dosimetry system each time. Another reason for
the low error ratios could be that the assumed uncertainties
were set too high. An improved uncertainty model could include nonisotropic positioning uncertainty rather than the 1
mm uncertainty for all degrees of freedom applied here.
Table IV showed that only few of the simulated applicator
displacement errors could be detected for patient 1. This was
due to the low doses per applicator 共less than 10 mGy for
most applicators兲 and dwell positions. Such low-level measurements are subject to a relatively large uncertainty contribution from variations of the background counting statistics
as illustrated by Fig. 2.
The good agreement between RL and OSL integral doses
in Fig. 3 shows that the RL signal was not substantially polluted by the so-called stem signal 共see Sec. II B兲 for any of
the five patients. From the calculated exposure of fiber cable
during the treatments it was estimated that the stem signal
affected the time-resolved RL dosimetry at any of the dwell
positions by less than 3% for patients 2–5. For patient 1,
however, we did assess that nine dwell positions could have
been affected by 10%–30%. The dwell times for these nine
dwell positions were less than 5 s, and they were therefore
not included in the dose verification shown in Table II. The
study shows that it remains relevant to reduce the stem effect
for the present instrumentation as discussed elsewhere.29 It
could also be of relevance to adapt a treatment-plan based
model of measurement uncertainty to account not only for
the potential influence of the stem effect but also for angular
response and detector energy dependence 共i.e., detectorsource distance兲.
IV.F. Practical aspects of online dose verification in a
clinical setting
The prototype system 共software and hardware兲 developed
during this study can essentially automatically record, analyze, and visualize the data online during an actual radiotherapy session. Ultimately, we imagine that such a system
could be used routinely for dose verification during PDR
treatments as follows: After the treatment planning and the
initiation of the plan, the radiophysicist would monitor that
the first pulse of the PDR brachytherapy is delivered with
good agreement between TPS predictions and in vivo measurements. This would be the prime dose verification. The
objective of measurements during subsequent treatment
pulses would primarily be to check the stability of the dose
delivery. Graphical visualization similar to Figs. 3 and 4
would probably be highly useful for the radiophysicist in the
process of resolving the reason for any measurement-plan
deviations and in the subsequent decision making. Although
this study demonstrates certain potentially beneficial features
5042
Andersen et al.: Time-resolved in vivo luminescence dosimetry for brachytherapy
of the suggested protocol, it should be stressed that in vivo
dosimetry is associated with a certain work load which may
or may not be justified given available resources and the
actual risk of errors.
V. CONCLUSIONS
It has been demonstrated that it is feasible to conduct
online time-resolved in vivo dosimetry using the RL/OSL
signals from fiber-coupled Al2O3 : C probes placed in standard brachytherapy stainless steel/titanium needles. Timeresolved measurements were found to provide a good way to
visualize the progression and stability of the treatments.
For three of the patients, we found no significant differences 共P ⬎ 0.01兲 for comparisons between in vivo measurements and calculated reference values at the level of dose per
dwell position, dose per applicator, or total dose per pulse.
For the two other patients, we noted significant deviations
for three individual pulses and for one dosimeter probe.
These deviations could have been due to applicator movement during the treatment and one incorrectly positioned dosimeter probe, respectively.
Computer simulations showed that the likelihood of detecting a pair of interchanged guide tubes increased by a
factor of 10 or more for the considered patients when going
from integrating to time-resolved dose verification. The likelihood of detecting a ⫾15 mm displacement error increased
by a factor of 1.5 or more. The ability to detect errors increased if the average source-to-probe distance was small
共for example, less than 25 mm兲. Dose verification may be
carried out for all individual dwell positions, but in the absence of a communication link between afterloader and doseverification system 共to identify dwell positions during the
treatment兲 it may be best to limit the dose verification to test
only the dose for each individual applicator.
ACKNOWLEDGMENTS
This work was supported by the Danish Medical Research
Council 共FSS兲 under the contract “Improved safety and precision of cancer treatment with radioactive sources,” the
Danish Cancer Society, the Danish Council for Strategic Research, and CIRRO—the Lundbeck Foundation Centre for
Interventional Research in Radiation Oncology. The authors
would also like to thank Dr. M. S. Akselrod, Stillwater Crystal Growth Division, Landauer Inc., USA for the Al2O3 : C
crystals.
a兲
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