Lucy Elizabeth Kershaw1,2, Andrew McPartlin2,3, Ben Taylor4, Ananya Choudhury2,3, and Marcel van Herk2
1CMPE, The Christie NHSFT, Manchester, United Kingdom, 2Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom, 3Oncology, The Christie NHSFT, Manchester, United Kingdom, 4Radiology, The Christie NHSFT, Manchester, United Kingdom
Synopsis
In this pilot work, our aim was to measure plasma
flow (Fp) and permeability-surface area product (PS) through the course of RT in
prostate tumour and normal tissue to determine whether significant changes
could be detected early in treatment.
We detected significant increases in Fp and
PS during radiotherapy in this small patient group.Introduction
Dynamic contrast-enhanced (DCE) MRI DCE enables
non-invasive characterisation of tissue microvasculature and has been used in multiple
cancers sites to assess treatment response [1]. Although prostate cancer is the
fourth most common cancer worldwide, with 1.1 million cases diagnosed in 2012
[2], there is little published data assessing DCE-MRI parameter changes during radiotherapy
(RT) in this group.
In this pilot work, our aim was to measure plasma
flow (F
p) and permeability-surface area product (PS) through the course of RT in
prostate tumour and normal tissue to determine whether significant changes
could be detected early in treatment, to test feasibility for potential future
biologically adaptive radiotherapy.
Patients and Methods
Fifteen patients with prostate cancer stage
T2b or greater were recruited after 3 months of androgen deprivation therapy,
and subsequently received 60 Gy of RT in 20 fractions. Each patient underwent three MRI
examinations: (1) before RT (2) during the 3rd week of RT (3) 8
weeks after the start of RT. Patients
were imaged at 1.5 T (Achieva, Philips Medical Systems, Best, The Netherlands)
using the cardiac coil and a flat perspex table top (made in-house) to match
the radiotherapy treatment position. An
imaging volume 400 x 400 x 100 mm was chosen, with the prostate toward the
inferior slices. The MR examination
began with high resolution T2w imaging (TSE, TR/TE=4800/120 ms, matrix 560 x
560 x 20), then all subsequent images were acquired with matrix 176x176x20
(overcontiguous slices) and SENSE factor 2.5 in the PE (LR) direction. Inversion-recovery turbo field echo (IRTFE)
was used to measure T
1 (TR/TE/α=2.38/0.77 ms/12°, shot interval 4 s, ETL=51, TI
= 64, 250, 1000, 2500, 3900 ms), and was followed by DCE-MRI images (turbo
field echo TR/TE/α =2.47/0.86 ms/30°, temporal resolution 1.2 s for 260 time
points) acquired during injection of 0.2 ml/kg gadoterate meglumine at 2 ml/s
followed by a saline chaser. The AIF was
extracted from the external iliac artery at each visit, T1 was estimated from
fitting to the IRTFE data, signal-intensity vs time curves were converted to
contrast agent concentration vs time curves and finally the AATH model [3] was
fitted on a voxelwise basis using in house-software (Python 3.4). Haematocrit was assumed to be 0.4. The dominant tumour lesion (DIPL), peripheral
zone (PZ) and central zone (CZ) were outlined by a radiologist and oncologist
with special interest in prostate multiparametric MRI on high-resolution T
2w
images and regions were transferred to the parameter maps to evaluate microvascular
parameters in each ROI. The Wilcoxon
signed ranks test was used to assess significance of the parameter changes
across time points, and the Mann-Whitney U test was used to assess differences
between regions at each visit.
Results
Thirteen patients completed all three
scans. One patient had the first scan
only, and one patient did not have the third scan. One patient had no identifiable area of
normal CZ. Box plots for F
p (figure 1)
and PS (figure 2) are shown for the DIPL, CZ and PZ across the three
visits. P-values for paired tests
between visits and Mann-Whitney U tests between regions at each visit are shown
in table 1, with p<0.05 considered significant.
Discussion
Our measurements show considerable
variation in parameters between patients after androgen deprivation therapy,
consistent with other studies [4,5].
Early increases in measures of perfusion and permeability during RT are
consistent with previous work in other tumours.
An increase in K
trans (a DCE-MRI parameter that combines information
about plasma flow and vessel permeability) has been shown in cervix tumours
early in radiotherapy treatment [6,7] and also in animal models, where
perfusion was measured using laser Doppler imaging [8]. Following this initial increase values return
towards baseline 8 weeks after RT. The
increased range in values seen early in treatment may indicate a variable
response to therapy. Early identification of radioresistant disease would allow
consideration of dose escalation or alternative treatment strategies. In future work, the other microvascular
parameters estimated using this model (e.g. plasma volume) will be investigated,
along with parameter heterogeneity.
Conclusion
We have detected significant changes in F
p
and PS during radiotherapy in this small patient group. If non-responders could be identified early
in RT treatment this may allow selected dose escalation and minimised treatment
associated toxicity. We intend to correlate changes with surrogate outcome
measures such as nadir PSA and biochemical failure when these data become
available.
Acknowledgements
WMIC radiographers, University of
Manchester Magnetic Resonance Imaging Facility grant for scan time.References
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