Prostate Cancer: DCE-MRI parameter changes during radiotherapy
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 (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, 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 T1 (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 T2w 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 Fp (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 Ktrans (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 Fp 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

[1] Sonia P, Padhani AR. Tumor response assessments with diffusion and perfusion MRI. Journal of Magnetic Resonance Imaging 2012; 35 (4), 745-763

[2] Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr (link is external), accessed December 2013

[3] St Lawrence KS, Lee TY. An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: I. Theoretical derivation. J Cereb Blood Flow Metab 1998;18(12):1378–85.

[4] Padhani AR, MacVicar a D, Gapinski CJ, et al. Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging. Radiology 2001;218(2):365–74.

[5] Alonzi R, Padhani AR, Taylor NJ, et al. Antivascular effects of neoadjuvant androgen deprivation for prostate cancer: an in vivo human study using susceptibility and relaxivity dynamic MRI. Int J Radiat Oncol Biol Phys 2011;80(3):721–7.

[6] Kim J-H, Kim CK, Park BK, et al. Dynamic contrast-enhanced 3-T MR imaging in cervical cancer before and after concurrent chemoradiotherapy. Eur Radiol 2012;22(11):2533–9.

[7] Zahra MA, Tan LT, Priest AN, et al. Semiquantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging measurements predict radiation response in cervix cancer. Int J Radiat Oncol Biol Phys 2009;74(3):766–73.

[8] Crokart N, Jordan BF, Baudelet C, et al. Early reoxygenation in tumors after irradiation: Determining factors and consequences for radiotherapy regimens using daily multiple fractions. Int J Radiat Oncol 2005;63(3):901–10.

Figures

Figure 1: Box plot showing median, interquartile range, range and outliers for plasma flow (Fp) measured in the tumour (DIPL), central zone (CZ) and peripheral zone (PZ) across three visits

Figure 2: Box plot showing median, interquartile range, range and outliers for permeability surface-area product (PS) measured in the tumour (DIPL), central zone (CZ) and peripheral zone (PZ) across three visits

Table 1: p-values for Wilcoxon signed ranks and Mann-Whitney U tests for differences in parameters between and within visits. Non-significant differences (p>0.05) are greyed out.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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