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Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Image-guided radiotherapy reduces the risk of under-dosing high-risk prostate cancer extra-capsular disease and improves biochemical control

Authors: Per Munck af Rosenschold, Michael J. Zelefsky, Aditya P. Apte, Andrew Jackson, Jung Hun Oh, Elliot Shulman, Neil Desai, Margie Hunt, Pirus Ghadjar, Ellen Yorke, Joseph O. Deasy

Published in: Radiation Oncology | Issue 1/2018

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Abstract

Background

To determine if reduced dose delivery uncertainty is associated with daily image-guidance (IG) and Prostate Specific Antigen Relapse Free Survival (PRFS) in intensity-modulated radiotherapy (IMRT) of high-risk prostate cancer (PCa).

Methods

Planning data for consecutive PCa patients treated with IMRT (n = 67) and IG-IMRT (n = 35) was retrieved. Using computer simulations of setup errors, we estimated the patient-specific uncertainty in accumulated treatment dose distributions for the prostate and for posterolateral aspects of the gland that are at highest risk for extra-capsular disease. Multivariate Cox regression for PRFS considering Gleason score, T-stage, pre-treatment PSA, number of elevated clinical risk factors (T2c+, GS7+ and PSA10+), nomogram-predicted risk of extra-capsular disease (ECD), and dose metrics was performed.

Results

For IMRT vs. IG-IMRT, plan dosimetry values were similar, but simulations revealed uncertainty in delivered dose external to the prostate was significantly different, due to positioning uncertainties. A patient-specific interaction term of the risk of ECD and risk of low dose to the ECD (p = 0.005), and the number of elevated clinical risk factors (p = 0.008), correlate with reduced PRFS.

Conclusions

Improvements in PSA outcomes for high-risk PCa using IG-IMRT vs. IMRT without IG may be due to improved dosimetry for ECD.
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Literature
1.
go back to reference Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer. 2007;7(12):949–60.CrossRefPubMed Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer. 2007;7(12):949–60.CrossRefPubMed
2.
go back to reference Meijer GJ, de Klerk J, Bzdusek K, van den Berg HA, Janssen R, Kaus MR, et al. What CTV-to-PTV margins should be applied for prostate irradiation? Four-dimensional quantitative assessment using model-based deformable image registration techniques. Int J Radiat Oncol Biol Phys. 2008;72(5):1416–25.CrossRefPubMed Meijer GJ, de Klerk J, Bzdusek K, van den Berg HA, Janssen R, Kaus MR, et al. What CTV-to-PTV margins should be applied for prostate irradiation? Four-dimensional quantitative assessment using model-based deformable image registration techniques. Int J Radiat Oncol Biol Phys. 2008;72(5):1416–25.CrossRefPubMed
3.
go back to reference Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2007;68(4):1053–8.CrossRefPubMed Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2007;68(4):1053–8.CrossRefPubMed
4.
go back to reference Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O, et al. 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(4):1028–33.CrossRefPubMed Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O, et al. 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(4):1028–33.CrossRefPubMed
5.
go back to reference Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002;53(5):1097–105.CrossRefPubMed Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002;53(5):1097–105.CrossRefPubMed
6.
go back to reference Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294(10):1233–9.CrossRefPubMed Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294(10):1233–9.CrossRefPubMed
7.
go back to reference Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006;24(13):1990–6.CrossRefPubMed Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006;24(13):1990–6.CrossRefPubMed
8.
go back to reference Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 2007;8(6):475–87.CrossRefPubMed Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 2007;8(6):475–87.CrossRefPubMed
9.
go back to reference de Crevoisier R, Tucker SL, Dong L, Mohan R, Cheung R, Cox JD, et al. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62(4):965–73.CrossRefPubMed de Crevoisier R, Tucker SL, Dong L, Mohan R, Cheung R, Cox JD, et al. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62(4):965–73.CrossRefPubMed
10.
go back to reference Heemsbergen WD, Hoogeman MS, Witte MG, Peeters ST, Incrocci L, Lebesque JV. Increased risk of biochemical and clinical failure for prostate patients with a large rectum at radiotherapy planning: results from the Dutch trial of 68 GY versus 78 Gy. Int J Radiat Oncol Biol Phys. 2007;67(5):1418–24.CrossRefPubMed Heemsbergen WD, Hoogeman MS, Witte MG, Peeters ST, Incrocci L, Lebesque JV. Increased risk of biochemical and clinical failure for prostate patients with a large rectum at radiotherapy planning: results from the Dutch trial of 68 GY versus 78 Gy. Int J Radiat Oncol Biol Phys. 2007;67(5):1418–24.CrossRefPubMed
11.
go back to reference Park SS, Yan D, McGrath S, Dilworth JT, Liang J, Ye H, et al. Adaptive image-guided radiotherapy (IGRT) eliminates the risk of biochemical failure caused by the bias of rectal distension in prostate cancer treatment planning: clinical evidence. Int J Radiat Oncol Biol Phys. 2012;83(3):947–52.CrossRefPubMed Park SS, Yan D, McGrath S, Dilworth JT, Liang J, Ye H, et al. Adaptive image-guided radiotherapy (IGRT) eliminates the risk of biochemical failure caused by the bias of rectal distension in prostate cancer treatment planning: clinical evidence. Int J Radiat Oncol Biol Phys. 2012;83(3):947–52.CrossRefPubMed
12.
go back to reference 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(2):388–91.CrossRefPubMed 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(2):388–91.CrossRefPubMed
13.
go back to reference Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Sperling D, Pei X, et al. Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(1):125–9.CrossRefPubMed Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Sperling D, Pei X, et al. Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(1):125–9.CrossRefPubMed
14.
go back to reference Wortel RC, Incrocci L, Pos FJ, van der Heide UA, Lebesque JV, Aluwini S, et al. Late side effects after image guided intensity modulated radiation therapy compared to 3D-conformal radiation therapy for prostate cancer: results from 2 prospective cohorts. Int J Radiat Oncol Biol Phys. 2016;95(2):680–9.CrossRefPubMed Wortel RC, Incrocci L, Pos FJ, van der Heide UA, Lebesque JV, Aluwini S, et al. Late side effects after image guided intensity modulated radiation therapy compared to 3D-conformal radiation therapy for prostate cancer: results from 2 prospective cohorts. Int J Radiat Oncol Biol Phys. 2016;95(2):680–9.CrossRefPubMed
15.
go back to reference Sveistrup J, af Rosenschold PM, Deasy JO, Oh JH, Pommer T, Petersen PM, et al. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Radiat Oncol. 2014;9:44.CrossRefPubMedPubMedCentral Sveistrup J, af Rosenschold PM, Deasy JO, Oh JH, Pommer T, Petersen PM, et al. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Radiat Oncol. 2014;9:44.CrossRefPubMedPubMedCentral
16.
go back to reference Yossepowitch O, Bjartell A, Eastham JA, Graefen M, Guillonneau BD, Karakiewicz PI, et al. Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences. Eur Urol. 2009;55(1):87–99.CrossRefPubMed Yossepowitch O, Bjartell A, Eastham JA, Graefen M, Guillonneau BD, Karakiewicz PI, et al. Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences. Eur Urol. 2009;55(1):87–99.CrossRefPubMed
17.
go back to reference Steuber T, Graefen M, Haese A, Erbersdobler A, Chun FK, Schlom T, et al. Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy. J Urol. 2006;175(3 Pt 1):939–44. discussion 44CrossRefPubMed Steuber T, Graefen M, Haese A, Erbersdobler A, Chun FK, Schlom T, et al. Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy. J Urol. 2006;175(3 Pt 1):939–44. discussion 44CrossRefPubMed
18.
go back to reference Chao KK, Goldstein NS, Yan D, Vargas CE, Ghilezan MI, Korman HJ, et al. Clinicopathologic analysis of extracapsular extension in prostate cancer: should the clinical target volume be expanded posterolaterally to account for microscopic extension? Int J Radiat Oncol Biol Phys. 2006;65(4):999–1007.CrossRefPubMed Chao KK, Goldstein NS, Yan D, Vargas CE, Ghilezan MI, Korman HJ, et al. Clinicopathologic analysis of extracapsular extension in prostate cancer: should the clinical target volume be expanded posterolaterally to account for microscopic extension? Int J Radiat Oncol Biol Phys. 2006;65(4):999–1007.CrossRefPubMed
19.
go back to reference Sohayda C, Kupelian PA, Levin HS, Klein EA. Extent of extracapsular extension in localized prostate cancer. Urology. 2000;55(3):382–6.CrossRefPubMed Sohayda C, Kupelian PA, Levin HS, Klein EA. Extent of extracapsular extension in localized prostate cancer. Urology. 2000;55(3):382–6.CrossRefPubMed
20.
go back to reference Zhang M, Moiseenko V, Liu M, Craig T. Internal fiducial markers can assist dose escalation in treatment of prostate cancer: result of organ motion simulations. Phys Med Biol. 2006;51(2):269–85.CrossRefPubMed Zhang M, Moiseenko V, Liu M, Craig T. Internal fiducial markers can assist dose escalation in treatment of prostate cancer: result of organ motion simulations. Phys Med Biol. 2006;51(2):269–85.CrossRefPubMed
21.
go back to reference Deasy JO, Blanco AI, Clark VH. CERR: a computational environment for radiotherapy research. Med Phys. 2003;30(5):979–85.CrossRefPubMed Deasy JO, Blanco AI, Clark VH. CERR: a computational environment for radiotherapy research. Med Phys. 2003;30(5):979–85.CrossRefPubMed
22.
go back to reference Munck Af Rosenschold P, Desai NB, Oh JH, Apte A, Hunt M, Kalikstein A, et al. Modeling positioning uncertainties of prostate cancer external beam radiation therapy using pre-treatment data. Radiother Oncol. 2014;110(2):251–5.CrossRefPubMedPubMedCentral Munck Af Rosenschold P, Desai NB, Oh JH, Apte A, Hunt M, Kalikstein A, et al. Modeling positioning uncertainties of prostate cancer external beam radiation therapy using pre-treatment data. Radiother Oncol. 2014;110(2):251–5.CrossRefPubMedPubMedCentral
23.
go back to reference Heemsbergen WD, Al-Mamgani A, Witte MG, van Herk M, Lebesque JV. Radiotherapy with rectangular fields is associated with fewer clinical failures than conformal fields in the high-risk prostate cancer subgroup: results from a randomized trial. Radiother Oncol. 2013;107(2):134–9.CrossRefPubMed Heemsbergen WD, Al-Mamgani A, Witte MG, van Herk M, Lebesque JV. Radiotherapy with rectangular fields is associated with fewer clinical failures than conformal fields in the high-risk prostate cancer subgroup: results from a randomized trial. Radiother Oncol. 2013;107(2):134–9.CrossRefPubMed
24.
go back to reference Witte MG, Heemsbergen WD, Bohoslavsky R, Pos FJ, Al-Mamgani A, Lebesque JV, et al. Relating dose outside the prostate with freedom from failure in the Dutch trial 68 Gy vs. 78 Gy. Int J Radiat Oncol Biol Phys. 2010;77(1):131–8.CrossRefPubMed Witte MG, Heemsbergen WD, Bohoslavsky R, Pos FJ, Al-Mamgani A, Lebesque JV, et al. Relating dose outside the prostate with freedom from failure in the Dutch trial 68 Gy vs. 78 Gy. Int J Radiat Oncol Biol Phys. 2010;77(1):131–8.CrossRefPubMed
25.
go back to reference van der Burgt M, Bergsma L, de Vries J, Pos FJ, Kalisvaart R, Heemsbergen W, et al. Impact of tumour invasion on seminal vesicles mobility in radiotherapy of prostate cancer. Radiother Oncol. 2015;117(2):283–7.CrossRefPubMed van der Burgt M, Bergsma L, de Vries J, Pos FJ, Kalisvaart R, Heemsbergen W, et al. Impact of tumour invasion on seminal vesicles mobility in radiotherapy of prostate cancer. Radiother Oncol. 2015;117(2):283–7.CrossRefPubMed
26.
go back to reference Butler WM, Merrick GS, Reed JL, Murray BC, Kurko BS. Intrafraction displacement of prone versus supine prostate positioning monitored by real-time electromagnetic tracking. J Appl Clin Med Phys. 2013;14(2):4141.CrossRefPubMed Butler WM, Merrick GS, Reed JL, Murray BC, Kurko BS. Intrafraction displacement of prone versus supine prostate positioning monitored by real-time electromagnetic tracking. J Appl Clin Med Phys. 2013;14(2):4141.CrossRefPubMed
27.
go back to reference Levegrun S, Jackson A, Zelefsky MJ, Venkatraman ES, Skwarchuk MW, Schlegel W, et al. Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer. Radiother Oncol. 2002;63(1):11–26.CrossRefPubMed Levegrun S, Jackson A, Zelefsky MJ, Venkatraman ES, Skwarchuk MW, Schlegel W, et al. Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer. Radiother Oncol. 2002;63(1):11–26.CrossRefPubMed
28.
go back to reference Bayley AJ, Catton CN, Haycocks T, Kelly V, Alasti H, Bristow R, et al. A randomized trial of supine vs. prone positioning in patients undergoing escalated dose conformal radiotherapy for prostate cancer. Radiother Oncol. 2004;70(1):37–44.CrossRefPubMed Bayley AJ, Catton CN, Haycocks T, Kelly V, Alasti H, Bristow R, et al. A randomized trial of supine vs. prone positioning in patients undergoing escalated dose conformal radiotherapy for prostate cancer. Radiother Oncol. 2004;70(1):37–44.CrossRefPubMed
29.
go back to reference Kupelian PA, Willoughby TR, Reddy CA, Klein EA, Mahadevan A. Impact of image guidance on outcomes after external beam radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70(4):1146–50.CrossRefPubMed Kupelian PA, Willoughby TR, Reddy CA, Klein EA, Mahadevan A. Impact of image guidance on outcomes after external beam radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70(4):1146–50.CrossRefPubMed
30.
go back to reference Dinh CV, Steenbergen P, Ghobadi G, Heijmink SW, Pos FJ, Haustermans K, et al. Magnetic resonance imaging for prostate cancer radiotherapy. Phys Med. 2016;32(3):446–51.CrossRefPubMed Dinh CV, Steenbergen P, Ghobadi G, Heijmink SW, Pos FJ, Haustermans K, et al. Magnetic resonance imaging for prostate cancer radiotherapy. Phys Med. 2016;32(3):446–51.CrossRefPubMed
Metadata
Title
Image-guided radiotherapy reduces the risk of under-dosing high-risk prostate cancer extra-capsular disease and improves biochemical control
Authors
Per Munck af Rosenschold
Michael J. Zelefsky
Aditya P. Apte
Andrew Jackson
Jung Hun Oh
Elliot Shulman
Neil Desai
Margie Hunt
Pirus Ghadjar
Ellen Yorke
Joseph O. Deasy
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-0978-1

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