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      Dosimetric impact of intrafraction motion on boosts on intraprostatic lesions: a simulation based on actual motion data from real time ultrasound tracking

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          Abstract

          Background

          Intrafraction motion is particularly problematic in case of small target volumes and narrow margins. Here we simulate the dose coverage of intraprostatic lesions (IPL) by simultaneous integrated boosts (SIB). For this purpose, we use a large sample of actual intrafraction motion data.

          Methods

          Fifty-three h of intra-fraction motion of the prostate were recorded in real-time by 4D ultrasound (4DUS) during 720 fractions in 28 patients. We simulate spherical IPLs with 3, 5, and 7 mm radius and matching spherical SIBs with 0, 2, and 5 mm safety margins. The volumetric overlap between IPLs and SIBs is calculated. Dose volume histograms (DVH) are estimated by Monte Carlo simulation.

          Results

          On average, the distance of the prostate was 1.3 mm from its initial position over all fractions and patients. Average volumetric overlap was 73, 82, and 87% of IPL volume in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 95% or more in case of 2 mm safety margins and 98% or more in case of 5 mm safety margins. DVHs showed that 80% of the IPL volume received 60, 72, and 79% of maximum dose in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 94% or more given moderately sized safety margins of 2 mm.

          Conclusions

          On average over all fractions and patients, the dose coverage would have been acceptable even for small target volumes such as IPLs of radius 3 to 7 mm and narrow fields. Moderate safety margins of 2 mm could have ensured a delivery of 90% or more of the SIB dose to the IPL. In this case, SIB volume would have been considerably larger than IPL volume, but still considerably smaller than the overall PTV of the prostate.

          Electronic supplementary material

          The online version of this article (10.1186/s13014-019-1285-1) contains supplementary material, which is available to authorized users.

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          Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial

          Laura Van den Bergh, Evelyn Monninkhof, Uulke A van der Heide … (2018)
          Article 0 comments Cited 52 times – based on 0 reviews     Review now
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            Inclusion of geometric uncertainties in treatment plan evaluation.

            Marcel van Herk, Peter Remeijer, Joos V Lebesque (2002)
            To correctly evaluate realistic treatment plans in terms of absorbed dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and tumor control probability (TCP) in the presence of execution (random) and preparation (systematic) geometric errors. The dose matrix is blurred with all execution errors to estimate the total dose distribution of all fractions. To include preparation errors, the CTV is randomly displaced (and optionally rotated) many times with respect to its planned position while computing the dose, EUD, and TCP for the CTV using the blurred dose matrix. Probability distributions of these parameters are computed by combining the results with the probability of each particular preparation error. We verified the method by comparing it with an analytic solution. Next, idealized and realistic prostate plans were tested with varying margins and varying execution and preparation error levels. Probability levels for the minimum dose, computed with the new method, are within 1% of the analytic solution. The impact of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV and planning target volume is adequate for three-field prostate treatments given the accuracy level in our department; i.e., the TCP in a population of patients, TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same TCP(pop). Only in regions with a high-dose gradient does such a margin reduction lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To give 90% of patients at least 98% EUD, the planning target volume margin must be approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the combined standard deviations of the preparation and execution errors. This recipe corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically reasonable values of Sigma and sigma. The new method computes in a few minutes the influence of geometric errors on the statistics of target dose and TCP(pop) in clinical treatment plans. Too small margins lead to a significant loss of TCP(pop) that is difficult to compensate for by dose escalation.
            Article 0 comments Cited 36 times – based on 0 reviews     Review now
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              Intra-fraction motion of the prostate is a random walk.

              H Ballhausen, Peter M M C Li, N-S Hegemann … (2015)
              A random walk model for intra-fraction motion has been proposed, where at each step the prostate moves a small amount from its current position in a random direction. Online tracking data from perineal ultrasound is used to validate or reject this model against alternatives. Intra-fraction motion of a prostate was recorded by 4D ultrasound (Elekta Clarity system) during 84 fractions of external beam radiotherapy of six patients. In total, the center of the prostate was tracked for 8 h in intervals of 4 s. Maximum likelihood model parameters were fitted to the data. The null hypothesis of a random walk was tested with the Dickey-Fuller test. The null hypothesis of stationarity was tested by the Kwiatkowski-Phillips-Schmidt-Shin test. The increase of variance in prostate position over time and the variability in motility between fractions were analyzed. Intra-fraction motion of the prostate was best described as a stochastic process with an auto-correlation coefficient of ρ = 0.92  ±  0.13. The random walk hypothesis (ρ = 1) could not be rejected (p = 0.27). The static noise hypothesis (ρ = 0) was rejected (p < 0.001). The Dickey-Fuller test rejected the null hypothesis ρ = 1 in 25% to 32% of cases. On average, the Kwiatkowski-Phillips-Schmidt-Shin test rejected the null hypothesis ρ = 0 with a probability of 93% to 96%. The variance in prostate position increased linearly over time (r(2) = 0.9  ±  0.1). Variance kept increasing and did not settle at a maximum as would be expected from a stationary process. There was substantial variability in motility between fractions and patients with maximum aberrations from isocenter ranging from 0.5 mm to over 10 mm in one patient alone. In conclusion, evidence strongly suggests that intra-fraction motion of the prostate is a random walk and neither static (like inter-fraction setup errors) nor stationary (like a cyclic motion such as breathing, for example). The prostate tends to drift away from the isocenter during a fraction, and this variance increases with time, such that shorter fractions are beneficial to the problem of intra-fraction motion. As a consequence, fixed safety margins (which would over-compensate at the beginning and under-compensate at the end of a fraction) cannot optimally account for intra-fraction motion. Instead, online tracking and position correction on-the-fly should be considered as the preferred approach to counter intra-fraction motion.
              Article 0 comments Cited 35 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Hendrik Ballhausen: +49.89.4400-54605 , Hendrik.Ballhausen@med.uni-muenchen.de
                Minglun Li: +49.89.4400-73760 , Minglun.Li@med.uni-muenchen.de
                Michael Reiner: +49.89.4400-76756 , Michael.Reiner@med.uni-muenchen.de
                Claus Belka: +49.89.4400-74521 , Claus.Belka@med.uni-muenchen.de
                Journal
                Journal ID (nlm-ta): Radiat Oncol
                Journal ID (iso-abbrev): Radiat Oncol
                Title: Radiation Oncology (London, England)
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1748-717X
                Publication date (Electronic): 16 May 2019
                Publication date PMC-release: 16 May 2019
                Publication date Collection: 2019
                Volume: 14
                Electronic Location Identifier: 81
                Affiliations
                ISNI 0000 0004 0477 2585, GRID grid.411095.8, Department of Radiation Oncology, , University Hospital, ; LMU Munich, Marchioninistrasse 15, 81377 Munich, Germany
                Article
                Publisher ID: 1285
                DOI: 10.1186/s13014-019-1285-1
                PMC ID: 6524311
                PubMed ID: 31096991
                SO-VID: 198bb6d1-9bd5-47c6-87c8-2dc0ec86d8de
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 18 October 2018
                Date accepted : 25 April 2019
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prostate cancer,intrafraction motion,intraprostatic lesion,simultaneous integrated boost,dosimetry,ultrasound
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prostate cancer, intrafraction motion, intraprostatic lesion, simultaneous integrated boost, dosimetry, ultrasound

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