Journal of Medical Imaging and Radiation Oncology 55 (2011) 304–310

RADIATIO N O N C O LO GY —O R I G I N A L ARTICLE jmiro_2272 304..310

A comparison of ICRU point doses and volumetric doses of

organs at risk (OARs) in brachytherapy for cervical cancer
Shalini K Vinod,1,2,3 Kate Caldwell,1 Annie Lau1 and Allan R Fowler1,2
1
Cancer Therapy Centre, Liverpool Hospital, 2University of New South Wales, and 3Collaboration for Cancer Outcomes, Research and Evaluation
(CCORE), Sydney, New South Wales, Australia

SK Vinod MBBS MD FRANZCR; K Caldwell B Abstract

App Sc (Medical Rad); A Lau B App Sc (Medical
Rad); AR Fowler MBBS FRANZCR. Introduction: In brachytherapy for cervix cancer, doses to organs at risk
(OARs) are traditionally calculated using the ICRU-38 point doses to rectum
Correspondence and bladder. Three-dimensional image-guided brachytherapy allows assess-
A/Professor Shalini Vinod, Cancer Therapy ment of OAR dose with dose volume histograms (DVHs). The purpose of this
Centre, Liverpool Hospital, Locked Bag 7103, study was to analyse the correlation between DVHs and ICRU point doses.
Liverpool BC, Sydney, NSW 1871, Australia. Methods: Using the PLATO™ planning system, the bladder, rectum and
Email: shalini.vinod@sswahs.nsw.gov.au sigmoid were retrospectively contoured on 62 CT datasets for 20 patients
treated with definitive radiotherapy. The median external beam radiotherapy
Conflicts of interest: The authors of this paper dose was 45 Gy. Brachytherapy was delivered using a CT-MRI compatible
have no actual or potential conflict of interests. tandem and ovoids to a median dose of 24 Gy in three fractions. DVHs were
calculated, and the minimum dose to 2 cc of tissue receiving the highest dose
Presentations: Presented at RANZCR Annual (D2cc) was recorded and compared with the ICRU point doses (DICRU).
Scientific Meeting 2009. Presented at the Results: The mean rectal DICRU was 4.01 Gy compared with D2cc of 4.28 Gy. The
Australasian Brachytherapy Group Meeting mean bladder DICRU was 6.74 Gy compared with D2cc of 8.65 Gy. The mean
2010. sigmoid D2cc was 4.58 Gy. The mean dose ratios (D2cc/DICRU) were 1.08 for
rectum and 1.39 for bladder. DICRU correlated with D2cc for rectum (r = 0.76,
Submitted 06 September 2010; accepted 21
P = 0.001) and for bladder (r = 0.78, P = 0.01).
December 2010.
Conclusion: OAR doses assessed by DVH criteria were higher than ICRU point
doses. The significant correlation between D2cc and DICRU has allowed us to set
doi:10.1111/j.1754-9485.2011.02272.x
DVH dose constraints for CT-based brachytherapy and thus begin the tran-
sition from two-dimensional to three-dimensional image-guided brachy-
therapy planning.

Key words: bladder; brachytherapy; cervix cancer; dose volume histogram;

radiotherapy planning; rectum.

Report 38) introduced recommendations for recording

Introduction and reporting doses to normal tissues through standard
Intracavitary brachytherapy (ICBT) plays a crucial role in ICRU bladder and rectal reference points.1 Despite this,
the management of carcinoma of the uterine cervix. It is there has been variable recording of these normal tissue
usually prescribed at the end of a course of external doses in brachytherapy planning.2,3
beam radiotherapy (EBRT) and is delivered via a central The integration of cross-sectional imaging modalities
intrauterine stent (tandem) and two ovoids or a ring (such as CT or MRI) into treatment planning for brachy-
applicator placed in the lateral vaginal fornices. Tradi- therapy has allowed for the development of a three-
tionally, treatment planning has been based on point dimensional (3D) image-based approach to prescribing
dose prescriptions (point A) and point estimates of doses and reporting. Since 2000, the Groupe Européen de
to organs at risk (OARs) using two-dimensional (2D) Curiethérapie / European Society for Therapeutic Radi-
radiographic images. In 1985, the International Com- ology and Oncology (GEC ESTRO) working group for
mission on Radiation Units and Measurements (ICRU gynaecological brachytherapy has established a 3D

© 2011 The Authors

304 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
 OAR volumetric doses in cervix brachytherapy

image-based treatment planning concept.4,5 The recom- was then densely packed into the vagina to fix the
mendations from the GEC ESTRO group include guide- applicator position and to displace the bladder and
lines for accurate delineation of gross tumour volume, rectum away from the vaginal applicators. Some cotton
definition and delineation of clinical target volume and ribbon was tied around the patients’ pelvis and then
planning target volume, as well as advice on delineating united with the applicators through the legs to help
OARs and assessing doses to these organs through dose stabilise the applicators during patient transfers. No sys-
volume histograms (DVHs).6 MRI is the preferred tematic prescription was given for bladder filling.
imaging modality to achieve precise delineation of target
volumes because of its superior image quality with excel-
Brachytherapy planning
lent soft tissue discrimination. However, MRI is not easily
accessible in many departments. Immediately before CT simulation, Selectron™ (Nucle-
In the absence of MRI, we chose to investigate the tron, Veenendaal, The Netherlands) source markers
usefulness of CT in the 3D image-based treatment plan- were inserted into the applicators to aid in the identifi-
ning approach. The OARs identified by the GEC ESTRO cation of the source positions on the images. With
group are the bladder, rectum and sigmoid colon, all of the patient in a supine position, a CT scan (Somatom
which can be accurately delineated on CT.7 The aim of Sensation 4, Siemens AG, Forchheim, Germany) of
this study was to evaluate OAR doses using DVHs and the pelvis was performed using 2-mm slices and
compare this with the traditional ICRU point doses and exported digitally to the Nucletron PLATO™ (Nucletron,
thereby determine DVH dose constraints to apply to Veenendaal, The Netherlands) treatment planning
future 3D image-based brachytherapy planning. system. A dose of 6–8 Gy was prescribed to point A.
In each case, using ICRU-38 guidelines, reference
points were introduced in treatment plans to calculate
Methods the ICRU bladder and rectal reference doses. Plans were
optimised if the ICRU bladder dose exceeded 75% or
Study population
rectal dose exceeded 70% of the prescribed dose. The
This was a retrospective analysis of 20 patients who under- ICRU bladder point was located at the most posterior
went curative radiotherapy with (n = 18) or without (n = 2) part of the Foley catheter balloon. The ICRU rectal point
concurrent cisplatin chemotherapy for cervical cancer was located at the level of the flange on the tandem, on
between July 2006 and April 2009. All patients underwent an antero-posterior line drawn through the tandem,
EBRT followed by ICBT. Eighteen patients had three ICBT 5 mm behind the posterior vaginal wall. In addition to
insertions, and two patients had four ICBT insertions. Each the ICRU points, doses to points 2.5, 5, 7.5 and 10 mm
insertion was evaluated separately. above and below these were also recorded. The
maximum dose (DMAX) to bladder and rectum was the
highest recorded dose at one of these points.
Radiotherapy
EBRT was given to all patients using 6/18 MV photons
Contouring OARs
with a 3D conformal four-field box technique. All patients
received a minimum dose of 45 Gy in 25 fractions. The Based on the GEC ESTRO guidelines, an atlas of con-
brachytherapy was commenced in the final week of touring of the rectum, bladder and sigmoid was created
EBRT, and ICBT fractions were performed a week apart. with input from a radiologist. The outer wall of the
To calculate the dose from combined EBRT and ICBT, it rectum was contoured from the ano-rectal sphincter
was assumed that the entire volume treated with (defined as 3 cm superior to the anal verge) to the
brachytherapy (including the OARs) received 100% of recto-sigmoid junction (defined by the change in direc-
the prescribed EBRT dose. tion of the bowel loops). The outer wall of the bladder
was contoured from the base of the contrast-filled Foley
catheter balloon to the superior most aspect of the
Intracavitary insertion
bladder. The outer wall of the sigmoid colon was con-
Each application was performed during general anaes- toured from the recto-sigmoid junction to the last slice in
thesia in the lithotomy position. A Foley catheter was which the uterine tandem could be visualised. The con-
inserted into the bladder, and 7 cc of radio-opaque touring was performed by radiation therapists and
contrast was injected into the balloon to aid in the checked by a radiation oncologist.
identification of the ICRU bladder reference point. A
gynaecological examination was performed, and the
Calculating DVHs
length of the uterine cavity was determined using a
uterine sound. The applicators used were Nucletron™ OAR DVHs were calculated by the PLATO™ treatment
(Nucletron, Veenendaal, the Netherlands) standard planning system following the assumption that the
CT/MR compatible tandem and ovoids. Vaseline gauze maximum dose was received by the same area of tissue

© 2011 The Authors

Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 305
SK Vinod et al.

for each brachytherapy fraction. The minimum dose to IIA in three, IIB in six and IIIB in six. Pathology
the highest irradiated 2 cc of sigmoid, rectum and was squamous cell carcinoma in 16 and adenocarcinoma
bladder was recorded (D2cc). This particular DVH was in four. The median age was 47 years (range, 31–71).
chosen as this is a reliable estimate of organ dose irre- EBRT doses given were 45 Gy in 25 fractions (n = 11),
spective of the method of OAR contouring (external 46.8 Gy in 26 fractions (n = 1), 50.4 Gy in 28 fractions
organ contour vs. organ wall contour).8 Other authors (n = 5), 54 Gy in 30 fractions (n = 2) and 55.8 Gy in 31
have also found good correlation between D2cc and ICRU fractions (n = 1). Doses higher than 45 Gy were deliv-
dose points (DICRU) for OAR8 although more often for the ered to smaller fields as a boost. The brachytherapy
rectum than the bladder.9,10 The equivalent dose in 2 Gy doses given were 28 Gy in four fractions (n = 2), 24 Gy
fractions (EQD2) was calculated using the linear qua- in three fractions (n = 15) and 22 Gy in three fractions
dratic equation with an a/b = 3. This conversion permit- (n = 3). In these three patients, the last fraction was
ted the doses for EBRT and ICBT to be added together to reduced to 6 Gy instead of 8 Gy because of high ICRU
calculate the total EQD2. The volumetric bladder and bladder or rectal doses.
rectum doses were then compared with the doses at the The mean dose to the rectum was 4.01 ⫾ 1.26 Gy at
bladder and rectum ICRU points. DICRU, 4.28 ⫾ 1.55 Gy for D2cc and 4.98 ⫾ 1.86 Gy at
DMAX. The mean EQD2 was 64.22 ⫾ 9.52 Gy at DICRU and
67.11 ⫾ 10.95 Gy for D2cc rectum. Figure 1 shows the
Statistical analysis
correlation between the DICRU and D2cc for the rectum
Statistical analysis was performed using SPSS statistical (rs = 0.76, P < 0.001), and Figure 2 shows the correla-
computer package version 15 (Chicago, IL). Bivariate tion between DMAX and D2cc for the rectum (rs = 0.61,
correlation was used to assess the relationship between P < 0.001). The mean dose ratio (D2cc/DICRU) for the
variables, and Pearson’s correlation coefficient was com- rectum was 1.08 (range, 0.69–2.64).
puted for these relationships. Scatter diagrams were The mean dose to the bladder was 6.74 ⫾ 2.76 Gy at
drawn to create a visual representation of these relation- DICRU, 8.65 ⫾ 2.41 Gy for D2cc and 8.05 ⫾ 2.99 Gy at
ships. Based on this, a ‘line of best fit’ was drawn to DMAX. The mean EQD2 was 92.63 ⫾ 26.60 Gy at DICRU and
specify a mathematical relationship between the vari- 110.46 ⫾ 24.06 Gy for D2cc bladder. Figure 3 shows the
ables. Results are presented as mean ⫾ 1 standard correlation between the DICRU and D2cc for the bladder
deviation. (rs = 0.78, P < 0.001), and Figure 4 shows the correla-
tion between DMAX and D2cc for the bladder (rs = 0.74,
P < 0.001). The mean dose ratio (D2cc/DICRU) for the
Results bladder was 1.39 (range, 0.87–3.35).
The FIGO (International Federation of Gynecology and The mean D2cc sigmoid was 4.58 ⫾ 1.72 Gy, and the
Obstetrics) stage of the 20 patients was IB in five, mean EQD2 was 70.40 ⫾ 13.05 Gy.

Fig. 1. Scatter diagram comparison of DICRU

and D2cc rectum. (rs = 0.76, P < 0.001). Line of
best fit: y = 0.6x + 2.

© 2011 The Authors

306 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
 OAR volumetric doses in cervix brachytherapy

Fig. 2. Scatter diagram comparison of DMAX

and D2cc rectum. (rs = 0.61, P < 0.001).

and so plans have been optimised if these doses exceed

Discussion acceptable limits. However, anatomically, these points
Brachytherapy for cervical cancer has traditionally been may not represent the maximum doses to these
planned using a 2D approach with orthogonal radio- organs.13 In the era of CT and MRI planning, contouring
graphs. The ICRU dose points to OAR are based on 2D of OAR is now possible with calculation of DVHs, as is
imaging and have been the standard for recording and standard practice in planning of EBRT. To move towards
reporting. These doses are related to late toxicities,11,12 implementation of image-based brachytherapy planning,

Fig. 3. Scatter diagram comparison of DICRU

and D2cc bladder. (rs = 0.78, P < 0.001). Line
of best fit: y = 1.17x - 2.7.

© 2011 The Authors

Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 307
SK Vinod et al.

Fig. 4. Scatter diagram comparison of DMAX

and D2cc bladder. (rs = 0.74, P < 0.001).

we performed a retrospective comparison of DVHs with D2cc rectum was similar to that reported by Kirisits et al.
ICRU dose points for OAR in cervical cancer. (for both types of applicators) and lower than reported
We found a significant correlation with the DICRU by Yaparpalvi using the Vienna applicator. It was also
rectum and D2cc rectum and DICRU bladder and D2cc within the dose constraint of D2cc rectum ⱕ75 Gy recom-
bladder. Our accepted DICRU of 5.6 Gy (70% point A mended by GEC ESTRO. The mean dose ratio (D2cc/DICRU)
dose) correlated to D2cc rectum of 6 Gy based on the ‘line of 1.08 shows that the D2cc dose is slightly higher than
of best fit’ on the scatter diagram. For the bladder, our the DICRU. This ratio was higher than that reported in
accepted DICRU of 6 Gy (75% point A dose) correlated to other studies (Table 1).6,9,10,15,16
D2cc bladder of 7.4 Gy. The GEC ESTRO dose volume The mean EQD2 for DICRU bladder was higher than that
constraints based on EQD2 are D2cc bladder ⱕ 90 Gy and reported in other studies with a difference of between 18
D2cc rectum ⱕ 75 Gy. When we applied this to our dose and 20 Gy (Table 1).6,15,16 This difference was even more
fractionation of 45 Gy in 25 fractions for external beam marked for D2cc bladder where the difference was
and 24 Gy in three fractions for brachytherapy, the 26–27 Gy. Although the aim was not to exceed bladder
calculated DVH constraints per fraction are D2cc DICRU of 6 Gy (for prescribed 8 Gy to point A), higher
rectum ⱕ 5.8 Gy and D2cc bladder ⱕ 7.3 Gy. These are doses were obviously accepted. However, there have
similar to the correlated doses from the scatter dia- been no grade 3 or 4 late bladder toxicities seen in this
grams. group of patients to date at short follow-up. The corre-
DICRU for both bladder and rectum underestimated DMAX sponding mean dose ratio (D2cc/DICRU) was similar to the
by 19% and 16%, respectively. Despite this the corre- study by Kirisits et al. using a similar applicators but
lation between D2cc and DMAX was no better than the higher than the studies using the Vienna applicator
correlation between D2CC and DICRU for both organs. D2cc (Table 1). Using low dose rate (LDR) brachytherapy,
rectum was less than DMAX rectum, but D2cc bladder was Pelloski et al. reported a higher mean dose ratio of 1.56
greater than DMAX bladder. Point doses in regions of steep with a mean difference of 6.8 Gy between bladder D2cc
dose gradients are becoming less clinically meaningful. and DICRU.10 However, none of these studies reported
D2CC is considered far more relevant for serious compli- bladder toxicity. In a separate study reporting on the
cations such as fistula formation.14 Vienna experience, Georg et al. found that D2cc corre-
The mean EQD2 for DICRU rectum was similar to other lated with severe bladder toxicity with a 15% risk of
studies using similar applicators (tandem and ring) and grade 2–4 toxicities for D2cc > 105 Gy.17 Our bladder
slightly lower than for those using the Vienna applicator doses fall within this range, and we will monitor toxicities
(Table 1).6,15,16 The Vienna applicator allows for needles with planned regular follow-up of these patients.
for interstitial implantation around the tandem, so it is Image-based brachytherapy remains in its infancy in
not surprising that the DICRU is higher. The mean EQD2 for Australia and New Zealand. A survey in 2009 revealed

© 2011 The Authors

308 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
 OAR volumetric doses in cervix brachytherapy

Table 1. Comparison with other studies

Current study Kirisits 20056 Yaparpalvi 200815 Kirisits 200616

n = 20 n = 22 n = 10 n = 22

62 datasets 76 datasets 30 datasets 50 datasets

Applicator type Tandem and ovoids Tandem and Ring Vienna applicator Vienna applicator
Imaging for planning CT MRI CT MRI
Prescribed dose (Gy)
External beam dose 45 40–45 45 45
External beam boost 0–10.8 0–15 9–14.4 0
Brachytherapy dose 3 ¥ 8 /4 ¥ 7 4–6 ¥ 7 3¥7 4¥7
Rectum
Mean EQD2 DICRU (Gy) 64 ⫾ 10 † 69 ⫾ 13 73 ⫾ 4 71 ⫾ 13
Mean EQD2 D2cc (Gy) 67 ⫾ 11 64 ⫾ 6 74 ⫾ 4 66 ⫾ 6
Mean ratio D2cc/DICRU 1.08 (0.69–2.64)‡ 0.92 (0.48–1.5) 1.01 (0.92–1.42) 0.93 (0.6–1.26)
Bladder
Mean EQD2 DICRU (Gy) 93 ⫾ 27 75 ⫾ 16 75 ⫾ 4 73 ⫾ 19
Mean EQD2 D2cc (Gy) 110 ⫾ 24 83 ⫾ 9 84 ⫾ 4 84 ⫾ 14
Mean ratio D2cc/DICRU 1.39 (0.87–3.35) 1.38 (0.71–3.07) 1.04 (0.82–2.12) 1.14 (0.71–3.07)
Sigmoid
Mean EQD2 D2cc (Gy) 70 ⫾ 13 63 ⫾ 7 – 67 ⫾ 7

†Figure represents mean ⫾ 1 standard deviation. ‡Figure in brackets represents range. CT, comput-
erised tomography; MRI, magnetic resonance imaging.

that only 20% of departments had adopted GEC

ESTRO guidelines for contouring and dose prescrip-
Acknowledgements
tion.18 Of these, only one department had access to We would like to thank David Sampson and Lucy Ohan-
MRI, the remainder relying on CT. To the best our essian for their help in contouring OARs, Shivani Kumar
knowledge, this is the first Australian study to report and Vikneswary Batumalai for assisting in statistical
on correlation of DVHs and ICRU points for OARs. We analysis and Dr Nira Borok for her advice in delineating
have attempted to contour intermediate and high-risk OARs for the contouring atlas.
clinical target volumes (CTV) on this patient cohort but
found it impossible because of the lack of soft tissue
definition and distortion from the applicators and References
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310 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists