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R E S E A R C H Open Access
Change in prostate volume during extreme
hypo-fractionation analysed with MRI
Adalsteinn Gunnlaugsson
1*
, Elisabeth Kjellén
1
, Oskar Hagberg
2
, Camilla Thellenberg-Karlsson
3
,
Anders Widmark
3
and Per Nilsson
4
Abstract
Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied
for prostate cancer. This demands a precise target definition and knowledge on target location and extension
during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment.
Our aim was to study prostate volume changes during extreme hypo-fractionation (7 × 6.1 Gy) by using
sequential MRIs.
Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective
randomized phase III trial. An MRI scan was done before startoftreatment,atmidtreatmentandattheendof
radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right,
anterior-posterior and cranial-caudal directions were measured.
Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to
baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most
pronounced in the anterior-posterior and cranial-caudal directions.
Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still
present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to
take into account when applying treatment margins during short extreme hypo-fractionation, and that tight
margins should be applied with caution.
Keywords: Hypo-fractionation, MRI, Prostate cancer, Radiotherapy, Swelling, Volume change
Background
The field of radiotherapy (RT) is rapidly evolving with new
advanced treatment techniques and improved imaging.
Implementation of magnetic resonance imaging (MRI) for
segmentation together with sophisticated image guided
radiotherapy (IGRT) techniques based on implanted fidu-
cials has resulted in improved accuracy and precision in
RT for prostate cancer [1-3]. A workflow based solely
on MR, i.e. from prostate delineation to treatment planning
and delivery, has been proposed and shown to reduce
systematic uncertainties considerably compared to a con-
ventional CT/MR-based workflow [4]. Evidence from pros-
tate cancer radiotherapy trials shows that dose-escalation
improves outcome [5-8] with limited increase in toxicity
[9,10]. The latter is partly due to a reduction of the CTV-
PTV margins compared with those applied when position-
ing the treatment beams based on skin marks or on bony
structures [11]. In addition, inter-fraction and intra-fraction
prostate motion have been studied extensively during
recent years [12-14]. However, the optimal CTV-PTV
margin in a specific setting is still debated [15]. When
the margin is reduced to as small as 3 mm, adequate
coverage of at least larger prostates seems to be jeopar-
dized [16,17].
The CTV-PTV margin should not only take setup
variations and tumour motion into account but also in-
clude any changes in the shape and size of the CTV [18].
Changes in prostate morphology during radiotherapy are
not well studied. There is some evidence that prostate
size increases slightly during the first week(s) after start
* Correspondence: adalsteinn.gunnlaugsson@skane.se
1
Department of Oncology, Skåne University Hospital, Lund University, 22185
Lund, Sweden
Full list of author information is available at the end of the article
© 2014 Gunnlaugsson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Gunnlaugsson et al. Radiation Oncology 2014, 9:22
http://www.ro-journal.com/content/9/1/22
of conventionally fractionated RT and then decreases
substantially during treatment and shrinks to below
baseline by the end of treatment [19,20].
Hypo-fractionated RT of prostate cancer has earned
increased attention due to a proposed low α/βvalue, close
to 1.5 Gy [21,22]. The application of higher fraction doses
might result in a larger change in prostate shape and size
as compared with conventional fractionation, since prostate
swelling is known to occur during brachytherapy [23,24].
Theaimofthepresentstudywastomeasureany
changes in prostate size during a course of extreme
hypo- fractionation delivered with external beam technique
by using sequential MRI scanning before, during and at
the end of the RT course. A cohort of patients from a
Swedish multicentre trial (HYPO-RT-PC), studying ex-
treme hypo-fractionation, was used for the study.
Methods
Patients
Twenty patients treated with extreme hypo-fractionation
were included in the present study. All patients were
recruited from an on-going Scandinavian prospective
randomized phase III trial (HYPO-RT-PC), which com-
pares extreme hypo-fractionation with conventional frac-
tionation in intermediate risk prostate cancer patients [25].
This study was approved by the local ethics committee
(Division of Oncology, Department of Clinical Sciences,
Lund University) and is performed according to the Helsinki
Declaration of 1975, (revised in 2000). Inclusion criteria
are: age < 75 years, WHO performance status 0–2, inter-
mediate risk prostate cancer with clinical category T1c-T3a
with one of the following risk factors: 1) T3a, 2) Gleason ≥
7or3)PSA>10μg/L. PSA shall be < 20 μg/L and a
biopsy-proven adenocarcinoma without any signs of spread
distally or to lymph nodes are also required. Any earlier
treatment for prostate cancer, previous hormonal therapy,
other serious diseases (including prior malignant disease),
conditions that could prevent implantation of markers into
the prostate or signs of metastatic disease are exclusion
criteria. Patient characteristics for the cohort in the present
study are given in Table 1.
Treatment
In the HYPO-RT-PC study, patients are randomized
between either conventional fractionation (39 × 2.0 Gy =
78.0 Gy given once a day, five days per week) or to an
experimental arm with an extreme hypo-fractionated
regimen (7 × 6.1 Gy = 42.7 Gy given every other weekday,
and always including two weekends without RT). The trial
arms are equieffective assuming α/β= 3 Gy, neglecting
any influence of the difference in total treatment time.
Both 3D-conform radiotherapy (3D-CRT) and IMRT/
VMAT techniques are allowed. Hormonal treatment is
not permitted.
Radiotherapy procedure according to the HYPO-RT-PC
study protocol
Three gold markers were implanted into the prostate for
daily image guidance at least three weeks before the treat-
ment planning CT to avoid post-implant oedema of the
gland. Target and OAR definitions were according to
ICRU [18,26,27]. The CTV, i.e. prostate (no seminal
vesicles), was segmented as visualised on the treatment-
planning CT (slice thickness ≤3 mm). CT defined prostate
segmentation is mandatory according to the study protocol
but MRI is recommended as an aid for target delineation.
The PTV includes CTV with a 7 mm isotropic 3D-margin.
The CT-based CTV volume for the patients included in the
present study was already defined within the clinical trial
by three different senior radiation oncologists.
Sequential MRI scanning for CTV delineation
The patients were imaged with a Siemens Espree 1.5 T
MR scanner (Siemens Medical, Erlangen, Germany) using
abodycoilandaT2weightedhigh-resolution3Dse-
quence with axial slices (slice thickness 1.7-3.3 mm).
This MRI sequence is used in clinical routine as aid for
the CT-based target definition. The patients were placed
in supine position with a leg fixation device on a flat table-
top insert during the MR imaging, i.e. in the same position
as for RT.
MRI scans were performed at baseline (MRI
baseline
)when
the patient came for treatment-planning CT, in the middle
(MRI
mid
, EQD2
3
= 33 Gy) and at the end of treatment
(MRI
end,
EQD2
3
= 67 Gy). The MRI studies were trans-
ferred to the treatment planning system (Nucletron Oncen-
tra, ver 4.0) where the prostate was delineated in each MRI
slice by the same radiation oncologist (AG). This delineation
was done in a blinded fashion. The volume, as calculated
by the treatment planning system, was registered for each
CTV
MRI
. In addition, the maximum extension of the
Table 1 Patient baseline characteristics (n = 20)
Age
Median (range) 68 (59–73)
Tumour stage
T1c 17
T2 3
Gleason score
63
714
83
iPSA (ng/mL)
Mean (SD) 10.2 (4.5)
Prostate volume (cm
3
)*
Mean (SD) 73 (30)
*As segmented on CT.
Gunnlaugsson et al. Radiation Oncology 2014, 9:22 Page 2 of 6
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delineated prostate on the MRIs was measured in the three
principal directions, i.e. left-right (x
max
), anterior-posterior
(y
max
) and cranial-caudal (z
max
) to estimate any changes in
size in the three directions. The x
max
,y
max
and z
max
values
are hence the sides of the smallest rectangular prism
which precisely contains the segmented prostate.
To test whether the average change in prostate volume at
the various time points was significant, a standard two-sided
t-test was used. A p-value < 0.05 was considered significant.
Results
Segmented absolute prostate volumes together with rela-
tive prostate volume changes vs. the baseline MRI volume
are given in Table 2. The results are also presented graphic-
ally in Figure 1. The prostate volumes measured on the
treatment-planning CT averaged 23% larger than those
delineated on the baseline MRI (MRI
baseline
). The differ-
ence was statistically significant, p = 0.0001.
The median time (range) elapsed from MRI
baseline
to
MRI
mid
and from MRI
baseline
to MRI
end
was 8 (6–9) days
and 16 (15–17) days, respectively. According to the sequen-
tial MRI scanning analyses, extreme hypo-fractionation
caused a 14% mean relative volume increase (p < 0.0001)
at MRI
mid
. The mean volume increase was still present
at the time of the last treatment fraction (9% at MRI
end
,
p = 0.0002). There was no significant difference in mean
relative volume change between prostates above vs. below
the median CTV size, neither at MRI
mid
(p = 0.30) nor at
MRI
end
(p = 0.20).
The maximum prostate dimensions (x
max
,y
max
and
z
max
) as defined above were unchanged in the lateral
direction but increased in the anterior-posterior and
cranial-caudal directions by 2–3mmforMRI
mid
or
MRI
end
as compared with baseline (see Table 3 for details).
Corresponding data for “small”versus “large”prostate
baseline volumes are presented in Table 4.
Discussion
Variations in prostate size during a course of radiother-
apy using conventional fractionation have been studied
Table 2 Prostate volumes in descending order as segmented on the treatment planning CT and on the MR images
before radiotherapy (MRI
baseline
), in the middle of the treatment (MRI
mid
) and at the end of treatment (MRI
end
)
Pat # CT MRI
baseline
MRI
mid
MRI
end
Abs. vol. (cm
3
) Rel. vol. Abs. vol. (cm
3
) Abs. vol. (cm
3
) Rel. vol. Abs. vol. (cm
3
) Rel. vol.
1 35.3 1.579 22.4 26.7 1.191 27.2 1.217
2 44.5 1.369 32.5 38.6 1.187 34.9 1.074
3 33.8 0.999 33.9 39.0 1.151 33.1 0.976
4 47.8 1.105 43.3 47.5 1.098 46.2 1.067
5 45.8 1.054 43.4 48.9 1.126 48.7 1.122
6 64.8 1.455 44.5 53.3 1.198 44.1 0.991
7 71.6 1.597 44.8 49.8 1.112 46.6 1.040
8 43.5 0.906 48.0 48.7 1.015 48.0 1.000
9 79.4 1.648 48.2 55.5 1.152 54.4 1.129
10 73.0 1.511 48.4 48.9 1.011 50.1 1.037
11 59.4 1.102 53.9 60.8 1.128 55.2 1.023
12 57.0 1.037 54.9 65.3 1.189 64.4 1.172
13 –
*
–
*
57.2 66.6 1.166 62.2 1.089
14 83.8 1.196 70.1 88.7 1.265 78.0 1.112
15 99.0 1.347 73.5 80.0 1.088 74.1 1.008
16 79.4 1.066 74.5 95.5 1.282 96.2 1.291
17 96.5 1.145 84.3 96.8 1.148 –
‡
–
‡
18 105.8 1.242 85.2 96.3 1.131 101.4 1.190
19 106.2 1.021 104.0 116.8 1.123 115.6 1.112
20 153.7 1.045 147.1 155.0 1.054 152.9 1.040
Mean 72.7 1.233 60.7 68.9 1.141 64.9 1.089
SD 30.4 0.232 28.7 31.3 0.070 31.9 0.084
p-value
†
0.0001 0.0004 —<0.0001 <0.0001 0.0008 0.0002
Relative volumes and p-values are in relation to MRI
baseline
.
*Prostate was not segmented on CT as the patient had a hip prosthesis.
‡
Missing data, MRI not performed.
†
Paired t-test.
Gunnlaugsson et al. Radiation Oncology 2014, 9:22 Page 3 of 6
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previously. Generally these studies have shown an overall
prostate volume reduction at end of treatment (without
any anti-hormonal treatment) as compared to baseline
although with an initial volume increase [19,20,28]. Based
on the relative position of implanted electro-magnetic
transponders, King et al. showed that the prostate size
increases transiently (mean 6.1%) during the first week(s)
after start of conventional RT (total dose 81 Gy, 1.8 Gy/
fraction) and then shrinks to below baseline by the end of
treatment. The decrease in mean prostate volume was
10.9% from the first to the final day of RT. Using MRI,
Nichol et al. studied changes in prostate size during
conventionally fractionated RT (total dose 79.8 Gy,
1.9 Gy/fraction) in 25 patients. They reported a prostate
volume decrease by 0.5%/fraction. Based on CT scanning
at start and at the last week of RT (total dose 76 Gy,
2.0 Gy/fraction), Sanguineti et al. reported a mean decrease
in prostate volume of 7% in 14 patients without any anti-
hormonal treatment.
To our knowledge there are no earlier studies on how
extreme hypo-fractionation affects the prostate volume
during radiotherapy. The extreme hypo-fractionation regi-
men used in our study lead to a significant increase in
prostate volume after three treatment fractions (EQD2
3
=
33 Gy). This increase was still apparent at the end of treat-
ment after six fractions (EQD2
3
= 67 Gy). Our observa-
tions indicate that the enlargement of the CTV is both
larger than that known for conventional therapy and
stays enlarged during the whole treatment course. This
could be an important factor to take into account when
choosing margin size.
When using daily imaging for set up correction, a mini-
mum margin size between 1.5-3 mm to compensate for
intra-fraction motion of the prostate has been proposed as
adequate [15,16]. Our results indicate that a margin exten-
sion of similar magnitude (covering the 95% CIs in Table 3)
could be needed to take prostate swelling into account dur-
ing extreme hypo-fractionation. The analysis of prostate
0,50
0,60
0,70
0,80
0,90
1,00
1,10
1,20
1,30
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
MRIbaseline
MRImid
MRIend
Figure 1 Relative prostate volume compared to baseline (MRI
baseline
) at MRI
mid
(EQD2
3
= 33 Gy) (squares) and at MRI
end
(EQD2
3
= 67 Gy) (circles) for patients 1–20.
Table 3 Average change in maximum prostate extension in lateral (Δx
max
), anterior–posterior (Δy
max
)andcranial–caudal
(Δz
max
) direction (mean values and 95% CI)
Δx
max
(mm) P Δy
max
(mm) p Δz
max
(mm) p
MR
mid
–MR
baseline
0.2 (−1.1–1.5) 0.72 3.3 (1.8–4.8) 0.0002 2.5 (1.0–3.9) 0.0019
MR
end
–MR
baseline
0.3 (−0.9–1.4) 0.60 2.0 (0.5–3.4) 0.010 2.0 (0.8–3.1) 0.0029
MR
end
–MR
mid
0.1 (−0.8–0.9) 0.89 −1.4 (−2.7–−0.1) 0.036 −0.6 (−1.7–0.6) 0.32
Gunnlaugsson et al. Radiation Oncology 2014, 9:22 Page 4 of 6
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distension showed that the prostate seemed to swell most
profoundly in the anterior-posterior and cranial-caudal
directions. This might indicate that a margin reduction
towards the rectum should be applied with caution, espe-
cially during extreme hypo-fractionation. The difference in
prostate expansion in cranial-caudal and anterior-posterior
directions on one hand and lateral direction on the other
hand could be due to the pelvic side wall acting as an
anatomic barrier [19].
Prostate swelling during brachytherapy is well known
[23,24], and thus one could expect larger swelling when
using hypo-fractionation than during conventional radio-
therapy treatment. Our study supports this and sparks
concerns that larger treatment margins are indicated with
this kind of regimen as compared with conventional treat-
ment, especially if prostate segmentation is based on MRI
only. MRI-based contouring at baseline resulted in a CTV
volume that was about 20% smaller than the volume
generated in the original treatment-planning CT which
is in concordance with an earlier study by Smith et al.
[29] who found an average difference of 16%. Inferior
soft tissue contrast on CT as compared to MRI increases
inter-observer variability in CT-based target definition
which can partly explain this difference in volume between
CT and MRI. The fact that current clinical evidence in
prostate cancer radiotherapy is generated from CT-based
target definition, implies that great care has to be taken to
compensate for prostate swelling if the segmentation and
treatment planning process is performed with MR-only
[30]. We also looked at whether patients with larger
prostate glands experienced more swelling than patients
with smaller glands. No such difference in relative prostate
volume change was observed.
To minimize multi-observer variation in prostate seg-
mentation as well as MRI-sequence based errors [31], the
same radiation oncologist did the delineation in a blinded
fashion on the same MRI-sequence at each time-point.
The fact that the prostate increased in volume at mid-
treatment as compared to baseline for all patients supports
that this is due to a true treatment induced swelling and
not a methodological error. One could also argue that
image guided set-up correction would cope with this
change in prostate shape during the course of treat-
ment. However, this correction usually involves three
markers implanted centrally in the prostate gland, and
thus it is probably adequate for prostate motion but less
adequate for taking changes in the outer boundaries of
the gland into consideration. Re-contouring of the prostate
volume followed by re-planning before each fraction could
be needed when using narrow margins (≤3mm).
Conclusions
Our study indicates that the prostate swells significantly
during external radiotherapy when using extreme hypo-
fractionation. This seems to be an important factor when
defining margin size for extreme hypo-fractionation sched-
ules for prostate cancer to minimize the risk of treatment
failure when using narrow margins. In order to take
prostate swelling into account when using extreme hypo-
fractionation, we conclude that up to 2 mm extra margin
could be needed if prostate segmentation is based only on
MRI. Adaptive radiotherapy with re-planning before each
fraction, which would also take changes in prostate shape
into consideration, would be optimal.
We are planning a larger study on prostate volume
change within the frame of the HYPO-RT-PC trial also
including conventional fractionation for comparison.
Consent
Written informed consent was obtained from all patients
included in this study.
Competing interests
All authors declare that they have no competing interests.
Authors’contributions
AG, EK and PN designed the study, retrieved and analysed the data
and drafted the manuscript. OH gave statistical advice and revised
the manuscript. CTK and AW were involved in the study design and
revised the manuscript. All authors read and approved the final
manuscript.
Acknowledgements
We would like to thank Birgitta Bern and Nils-Olof Karlsson at the Department
of Radiotherapy in Umeå for all help with MRI scanning.
Author details
1
Department of Oncology, Skåne University Hospital, Lund University, 22185
Lund, Sweden.
2
Department of Epidemiology, Skåne University Hospital,
Lund University, 22185 Lund, Sweden.
3
Department of Oncology and
Department of Radiation Sciences, Umeå University Hospital, SE-901 85
Umeå, Sweden.
4
Department of Oncology and Radiation Physics, Skåne
University Hospital, Lund University, 22185 Lund, Sweden.
Received: 11 August 2013 Accepted: 3 January 2014
Published: 13 January 2014
Table 4 Average change in maximum prostate extension in lateral (Δx
max
), anterior–posterior (Δy
max
)andcranial–caudal
(Δz
max
) direction for “small”/“large”prostate volumes, i.e. below/above median MRI
baseline
volume (=50 cm
3
)
Δx
max
(mm) p Δy
max
(mm) p Δz
max
(mm) p
MR
mid
–MR
baseline
−0.5/1.0 0.24 3.3/3.3 0.98 1.9/3.0 0.44
MR
end
–MR
baseline
−0.1/0.7 0.44 1.3/2.8 0.29 1.9/2.0 0.88
MR
end
–MR
mid
0.0/0.0 0.41 −0.2/−0.1 0.24 0.0/−0.1 0.34
Gunnlaugsson et al. Radiation Oncology 2014, 9:22 Page 5 of 6
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References
1. Balter JM, Lam KL, Sandler HM, Littles JF, Bree RL, Ten Haken RK: Automated
localization of the prostate at the time of treatment using implanted
radiopaque markers: technical feasibility. Int J Radiat Oncol Biol Phys 1995,
33:1281–1286.
2. Balter JM, Chen GTY, Pelizzari CA, Krishnasamy S, Rubin S, Vijayakumar S:
Online repositioning during treatment of the prostate: a study of
potential limits and gains. Int J Radiat Oncol Biol Phys 1993, 27:137–143.
3. Ploeger LS, Frenay M, Betgen A, de Bois JA, Gilhuijs KG, van Herk M:
Application of video imaging for improvement of patient set-up.
Radiother Oncol 2003, 68:277–284.
4. Nyholm T, Nyberg M, Karlsson MG, Karlsson M: Systematisation of spatial
uncertainties for comparison between a MR and a CT-based radiotherapy
workflow for prostate treatments. Radiat Oncol 2009, 17(4):54.
5. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK,
Pollack A: Long-term results of the M. D. Anderson randomized dose-escalation
trial for prostate cancer. IntJRadiatOncolBiolPhys2008, 70:67–74.
6. Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O, Park J, Shippy
A: Long-term results of conformal radiotherapy for prostate cancer:
impact of dose escalation on biochemical tumor control and distant
metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 2008,
71:1028–1033.
7. Zelefsky MJ, Chou JF, Pei X, Yamada Y, Kollmeier M, Cox B, Zhang Z,
Schechter M, Cohen GN, Zaider M: Predicting biochemical tumor control
after brachytherapy for clinically localized prostate cancer: the memorial
Sloan-Kettering cancer center experience. Brachytherapy 2012, 11:245–249.
8. Michalski J, Winter K, Roach M, Markoe A, Sandler HM, Ryu J, Parliament M,
Purdy JA, Valicenti RK, Cox JD: Clinical outcome of patients treated with
3D conformal radiation therapy (3D-CRT) for prostate cancer on RTOG
9406. Int J Radiat Oncol Biol Phys 2012, 83:363–370.
9. Schulz RJ, Kagan AR: Dose escalation in the radiation therapy of prostate
cancer. Int J Radiat Oncol Biol Phys 2011, 80:1289–1291.
10. Fransson P, Bergstrom P, Lofroth P-O, Widmark A: Five-year prospective pa-
tient evaluation of bladder and bowel symptoms after dose-escalated
radiotherapy for prostate cancer with the BeamCath technique. Int J
Radiat Oncol Biol Phys 2006, 66:430–438.
11. van Herk M: Errors and margins in radiotherapy. Semin Radiat Oncol 2004,
14:52–64.
12. Ghilezan MJ, Jaffray DA, Siewerdsen JH, Van Herk M, Shetty A, Sharpe MB,
Zafar Jafri S, Vicini FA, Matter RC, Brabbins DS, Martinez AA: Prostate gland
motion assessed with cine-magnetic resonance imaging (cine-MRI). Int J
Radiat Oncol Biol Phys 2005, 62:406–417.
13. Malone S, Crook JM, Kendal WS, Zanto JS: Respiratory-induced prostate
motion: quantification and characterization. Int J Radiat Oncol Biol Phys
2000, 48:105–109.
14. Budiharto T, Slagmolen P, Haustermans K, Maes F, Junius S, Verstraete J,
Oyen R, Hermans J, Van den Heuvel F: Intrafractional prostate motion
during online image guided intensity-modulated radiotherapy for pros-
tate cancer. Radiother Oncol 2011, 98:181–186.
15. Enmark M, Korreman S, Nystrom H: IGRT of prostate cancer; is the margin
reduction gained from daily IG time-dependent? Acta Oncol 2006, 45:907–914.
16. Melancon AD, Daniel JC O, Zhang L, Kudchadker RJ, Kuban DA, Lee AK,
Cheung RM, de Crevoisier R, Tucker SL, Newhauser WD, Mohan R, Dong L:
Is a 3-mm intrafractional margin sufficient for daily image-guided
intensity-modulated radiation therapy of prostate cancer? Radiother
Oncol 2007, 85:251–259.
17. Engels B, Soete G, Verellen D, Storme G: Conformal arc radiotherapy for
prostate cancer: Increased biochemical failure in patients with distended
rectum on the planning computed tomogram despite image guidance
by implanted markers. Int J Radiat Oncol Biol Phys 2009, 74:388–391.
18. International Commission of Radiation Units and Measurements: ICRU report 83:
Prescribing, Recording, and Reporting Photon-Beam Intensity-Modulated
Radiation Therapy (IMRT). Journal of the ICRU 2010, 10:1.
19. King BL, Butler WM, Merrick GS, Kurko BS, Reed JL, Murray BC, Wallner KE:
Electromagnetic transponders indicate prostate size increase followed
by decrease during the course of external beam radiation therapy. Int J
Radiat Oncol Biol Phys 2010, 79:1350–1357.
20. Nichol AM, Brock KK, Lockwood GA, Moseley DJ, Rosewall T, Warde PR,
Catton CN, Jaffray DA: A magnetic resonance imaging study of prostate
deformation relative to implanted gold fiducial markers. Int J Radiat
Oncol Biol Phys. 2007, 67:48–56.
21. Miralbell R, Roberts SA, Zubizarreta E, Hendry JH: Dose-fractionation
sensitivity of prostate cancer deduced from radiotherapy outcomes of
5,969 patients in seven international institutional datasets: α/β= 1.4
(0.9-2.2) Gy. Int J Radiat Oncol Biol Phys 2012, 82:17–24.
22. Fowler J, Chappell R, Ritter M: Is alpha/beta for prostate tumours really
low? Int J Radiat Oncol Biol Phys 2001, 50:1021–1031.
23. Kono Y, Kubota K, Aruga T, Ishibashi A, Morooka M, Ito K, Itami J, Kanemura
M, Minowada S, Tanaka T: Swelling of the prostate gland by permanent
brachytherapy may affect seed migration. Jpn J Clin Oncol 2010,
40:1159–1165.
24. Chung E, Stenmark MH, Evans C, Narayana V, McLaughlin PW: Greater post-
implant swelling in small-volume prostate glands: Implications for dos-
imetry, treatment planning, and operating room technique. Int J Radiat
Oncol Biol Phys 2012, 82:1944–1948.
25. ISRCTN: Phase III study of HYPO-fractionated radiotherapy of intermedi-
ate risk localised prostate cancer. http://www.controlled-trials.com/
ISRCTN45905321.
26. International Commission of Radiation Units and Measurements, ICRU
report 50: Prescribing, Recording, and Reporting Photon-Beam Therapy.
Bethesda; 1993. ICRU; 1993 (ISBN 0-913394-48-3).
27. International Commission on Radiation Units and Measurements, ICRU report 62:
Prescribing, recording, and reporting photon beam therapy (supplement to ICRU
report 50). Bethesda; 1999. ICRU; 1999 (ISBN 0-913394-61-0).
28. Sanguineti G, Marcenaro M, Franzone P, Foppiano F, Vitale V: Neoadjuvant
androgen deprivation and prostate gland shrinkage during conformal
radiotherapy. Radiother Oncol 2003, 66:151–157.
29. Smith W, Lewis C, Bauman G, Rodrigues G, D'Souza D, Ash R, Ho D,
Venkatesan V, Downey D, Fenster A: Prostate volume contouring: a 3D
analysis of segmentation using 3DTRUS, CT, and MR. Int J Radiat Oncol
Biol Phys 2007, 67:1238–1247.
30. Jonsson JH, Karlsson MG, Karlsson M, Nyholm T: Treatment planning using
MRI data: an analysis of the dose calculation accuracy for different
treatment regions. Radiat Oncol 2010, 30:62.
31. Nyholm T, Jonsson J, Söderström K, Bergström P, Carlberg A, Frykholm G,
Behrens CF, Geertsen PF, Trepiakas R, Hanvey S, Sadozye A, Ansari J,
McCallum H, Frew J, McMenemin R, Zackrisson B: Radiat Oncol 2013, 24:126.
Epub ahead of print.
doi:10.1186/1748-717X-9-22
Cite this article as: Gunnlaugsson et al.:Change in prostate volume
during extreme hypo-fractionation analysed with MRI. Radiation Oncology
2014 9:22.
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