Minimum non-isotropic and asymmetric margins for taking into account intrafraction prostate motion during moderately hypofractionated radiotherapy


      • Time-dependent margins calculated for hypofractionated prostate cancer treatment.
      • The voxel shifting method was used to calculate non-isotropic and asymmetric margin.
      • Comparison with van Herk’s margin recipe was performed.
      • An auto-planning tool was used to assess the impact of prostate shift on CTV coverage.
      • Non Isotropic and asymetric margin is needed to ideally consider intrafraction motion.



      To investigate the impact on dose distribution of intrafraction motion during moderate hypofractionated prostate cancer treatments and to estimate minimum non-isotropic and asymmetric (NI-AS) treatment margins taking motion into account.


      Prostate intrafraction 3D displacements were recorded with a transperineal ultrasound probe and were evaluated in 46 prostate cancer patients (876 fractions) treated by moderate hypofractionated radiation therapy (60 Gy in 20 fractions). For 18 patients (346 fractions), treatment plans were recomputed increasing CTV-to-PTV margins from 0 to 6 mm with an auto-planning optimization algorithm. Dose distribution was estimated using the voxel shifting method by displacing CTV structure according to the retrieved movements. Time-dependent margins were finally calculated using both van Herk’s formula and the voxel shifting method.


      Mean intrafraction prostate displacements observed were −0.02 ± 0.52 mm, 0.27 ± 0.78 mm and −0.43 ± 1.06 mm in left–right, supero-inferior and antero-posterior directions, respectively. The CTV dosimetric coverage increased with increased CTV-to-PTV margins but it decreased with time. Hence using van Herk’s formula, after 7 min of treatment, a margin of 0.4 and 0.5 mm was needed in left and right, 1.5 and 0.7 mm in inferior and superior and 1.1 and 3.2 mm in anterior and posterior directions, respectively. Conversely, using the voxel shifting method, a margin of 0 mm was needed in left–right, 2 mm in superior, 3 mm in inferior and anterior and 5 mm in posterior directions, respectively. With this latter NI-AS margin strategy, the dosimetric target coverage was equivalent to the one obtained with a 5 mm homogeneous margin.


      NI-AS margins would be required to optimally take into account intrafraction motion.


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        • Hegemann N.S.
        • Guckenberger M.
        • Belka C.
        • Ganswindt U.
        • Manapov F.
        • Li M.
        Hypofractionated radiotherapy for prostate cancer.
        Radiat Oncol. 2014; 9
        • Benjamin L.C.
        • Tree A.C.
        • Dearnaley D.P.
        The Role of Hypofractionated Radiotherapy in Prostate Cancer.
        Curr Oncol Rep. 2017; 19: 30
        • Clemente S.
        • Nigro R.
        • Oliviero C.
        • Marchioni C.
        • Esposito M.
        • Giglioli F.R.
        • et al.
        Role of the technical aspects of hypofractionated radiation therapy treatment of prostate cancer: A review.
        Int J Radiat Oncol Biol Phys. 2015; 91: 182-195
        • Widmark A.
        • Gunnlaugsson A.
        • Beckman L.
        • Thellenberg-Karlsson C.
        • Hoyer M.
        • Lagerlund M.
        • et al.
        Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial.
        Lancet. 2019; 394: 385-395
        • Litzenberg D.W.
        • Balter J.M.
        • Hadley S.W.
        • Sandler H.M.
        • Willoughby T.R.
        • Kupelian P.A.
        • et al.
        Influence of intrafraction motion on margins for prostate radiotherapy.
        Int J Radiat Oncol Biol Phys. 2006; 65: 548-553
        • Chen Z.
        • Yang Z.
        • Wang J.
        • Hu W.
        Dosimetric impact of different bladder and rectum filling during prostate cancer radiotherapy.
        Radiat Oncol. 2016; 11
        • Li J.S.
        • Lin M.-H.
        • Buyyounouski M.K.
        • Horwitz E.M.
        • Ma C.-M.
        Reduction of prostate intrafractional motion from shortening the treatment time.
        Phys Med Biol. 2013; 58: 4921-4932
        • Lovelock D.M.
        • Messineo A.P.
        • Cox B.W.
        • Kollmeier M.A.
        • Zelefsky M.J.
        Continuous monitoring and intrafraction target position correction during treatment improves target coverage for patients undergoing sbrt prostate therapy.
        Int J Radiat Oncol Biol Phys. 2015; 91: 588-594
        • Langen K.M.
        • Willoughby T.R.
        • Meeks S.L.
        • Santhanam A.
        • Cunningham A.
        • Levine L.
        • et al.
        Observations on Real-Time Prostate Gland Motion Using Electromagnetic Tracking.
        Int J Radiat Oncol Biol Phys. 2008; 71: 1084-1090
        • Baker M.
        • Behrens C.F.
        Determining intrafractional prostate motion using four dimensional ultrasound system.
        BMC Cancer. 2016; 16
        • Sihono D.S.K.
        • Ehmann M.
        • Heitmann S.
        • von Swietochowski S.
        • Grimm M.
        • Boda-Heggemann J.
        • et al.
        Determination of Intrafraction Prostate Motion During External Beam Radiation Therapy With a Transperineal 4-Dimensional Ultrasound Real-Time Tracking System.
        Int J Radiat Oncol Biol Phys. 2018; 101
        • Richardson A.K.
        • Jacobs P.
        Intrafraction monitoring of prostate motion during radiotherapy using the Clarity® Autoscan Transperineal Ultrasound (TPUS) system.
        Radiography. 2017; 23: 310-313
        • de Muinck Keizer D.M.
        • Kerkmeijer L.G.W.
        • Willigenburg T.
        • van Lier A.L.H.M.W.
        • Hartogh M.D.D.
        • van der Voort van Zyp J.R.N.
        • et al.
        Prostate intrafraction motion during the preparation and delivery of MR-guided radiotherapy sessions on a 1.5T MR-Linac.
        Radiother Oncol. 2020; 151: 88-94
        • Herschtal A.
        • Foroudi F.
        • Silva L.
        • Gill S.
        • Kron T.
        Calculating geometrical margins for hypofractionated radiotherapy.
        Phys Med Biol. 2012; 58: 319-333
        • Vanhanen A.
        • Poulsen P.
        • Kapanen M.
        Dosimetric effect of intrafraction motion and different localization strategies in prostate SBRT.
        Phys Medica. 2020; 75: 58-68
        • van Herk M.
        • Remeijer P.
        • Rasch C.
        • Lebesque J.V.
        The probability of correct target dosage: Dose-population histograms for deriving treatment margins in radiotherapy.
        Int J Radiat Oncol Biol Phys. 2000; 47: 1121-1135
        • Pang E.P.P.
        • Knight K.
        • Fan Q.
        • Tan S.X.F.
        • Ang K.W.
        • Master Z.
        • et al.
        Analysis of intra-fraction prostate motion and derivation of duration-dependent margins for radiotherapy using real-time 4D ultrasound. Phys Imaging.
        Radiat Oncol. 2018; 5: 102-107
        • Unkelbach J.
        • Alber M.
        • Bangert M.
        • Bokrantz R.
        • Chan T.C.Y.
        • Deasy J.O.
        • et al.
        Robust radiotherapy planning.
        Phys Med Biol. 2018; 63: 22TR02
        • Biston M.-C.
        • Costea M.
        • Gassa F.
        • Serre A.-A.
        • Voet P.
        • Larson R.
        • et al.
        Evaluation of fully automated a priori MCO treatment planning in VMAT for head-and-neck cancer.
        Phys Medica. 2021; 87: 31-38
        • Richter A.
        • Exner F.
        • Weick S.
        • Lawrenz I.
        • Polat B.
        • Flentje M.
        • et al.
        Evaluation of intrafraction prostate motion tracking using the Clarity Autoscan system for safety margin validation.
        Z Med Phys. 2020; 30: 135-141
        • Pang E.P.P.
        • Knight K.
        • Park S.Y.
        • Lian W.
        • Master Z.
        • Baird M.
        • et al.
        Duration-dependent margins for prostate radiotherapy—a practical motion mitigation strategy.
        Strahlentherapie Und Onkol. 2020; 196: 657-663
        • Lachaine M.
        • Falco T.
        Intrafractional prostate motion management with the Clarity Autoscan system.
        Med Phys Int. 2013; 1
        • Vanherk M.
        Errors and margins in radiotherapy.
        Seminars Radiat Oncol. 2004; 14: 52-64
        • Brand D.H.
        • Tree A.C.
        • Ostler P.
        • van der Voet H.
        • Loblaw A.
        • Chu W.
        • et al.
        Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.
        Lancet Oncol. 2019; 20: 1531-1543
        • Xie Y.
        • Djajaputra D.
        • King C.R.
        • Hossain S.
        • Ma L.
        • Xing L.
        Intrafractional Motion of the Prostate During Hypofractionated Radiotherapy.
        Int J Radiat Oncol Biol Phys. 2008; 72: 236-246
        • Li J.S.
        • Jin L.
        • Pollack A.
        • Horwitz E.M.
        • Buyyounouski M.K.
        • Price R.A.
        • et al.
        Gains From Real-Time Tracking of Prostate Motion During External Beam Radiation Therapy.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1613-1620
      1. Li M, Hegemann N-S, Manapov F, Kolberg A, Thum PD, Ganswindt U, et al. Prefraction displacement and intrafraction drift of the prostate due to perineal ultrasound probe pressure. Strahlentherapie Und Onkol 2017;193.

        • Steiner E.
        • Georg D.
        • Goldner G.
        • Stock M.
        Prostate and patient intrafraction motion: Impact on treatment time-dependent planning margins for patients with endorectal balloon.
        Int J Radiat Oncol Biol Phys. 2013; 86: 755-761
        • Sumida I.
        • Yamaguchi H.
        • Das I.J.
        • Anetai Y.
        • Kizaki H.
        • Aboshi K.
        • et al.
        Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy.
        PLoS ONE. 2017; 12: e0173643
        • Li H.S.
        • Chetty I.J.
        • Solberg T.D.
        Quantifying the interplay effect in prostate IMRT delivery using a convolution-based method.
        Med Phys. 2008; 35: 1703-1710
        • Lee L.
        • Mao W.
        • Xing L.
        The use of EPID-measured leaf sequence files for IMRT dose reconstruction in adaptive radiation therapy.
        Med Phys. 2008; 35: 5019-5029
        • Schreibmann E.
        • Dhabaan A.
        • Elder E.
        • Fox T.
        Patient-specific quality assurance method for VMAT treatment delivery.
        Med Phys. 2009; 36: 4530-4535
        • Litzenberg D.W.
        • Hadley S.W.
        • Tyagi N.
        • Balter J.M.
        • Ten Haken R.K.
        • Chetty I.J.
        Synchronized dynamic dose reconstruction.
        Med Phys. 2007; 34: 91-102
        • Kontaxis C.
        • de Muinck Keizer D.M.
        • Kerkmeijer L.G.W.
        • Willigenburg T.
        • den Hartogh M.D.
        • van der Voort van Zyp J.R.N.
        • et al.
        Delivered dose quantification in prostate radiotherapy using online 3D cine imaging and treatment log files on a combined 1.5T magnetic resonance imaging and linear accelerator system.
        Phys Imaging Radiat Oncol. 2020; 15: 23-29
        • Zelefsky M.J.
        • Levin E.J.
        • Hunt M.
        • Yamada Y.
        • Shippy A.M.
        • Jackson A.
        • et al.
        Incidence of Late Rectal and Urinary Toxicities After Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy for Localized Prostate Cancer.
        Int J Radiat Oncol Biol Phys. 2008; 70: 1124-1129