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      The physics of radioembolization

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          Abstract

          Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.

          In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.

          This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.

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          Most cited references114

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          21 years of biologically effective dose.

          In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for "biologically equivalent dose", from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be "triangulated" to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion "How Fractionation Really Works". BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation.
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            An evidence-based review of quantitative SPECT imaging and potential clinical applications.

            SPECT has traditionally been regarded as nonquantitative. Advances in multimodality γ-cameras (SPECT/CT), algorithms for image reconstruction, and sophisticated compensation techniques to correct for photon attenuation and scattering have, however, now made quantitative SPECT viable in a manner similar to quantitative PET (i.e., kBq cm(-3), standardized uptake value). This review examines the evidence for quantitative SPECT and demonstrates clinical studies in which the accuracy of the reconstructed SPECT data has been assessed in vivo. SPECT reconstructions using CT-based compensation corrections readily achieve accuracy for (99m)Tc to within ± 10% of the known concentration of the radiotracer in vivo. Quantification with other radionuclides is also being introduced. SPECT continues to suffer from poorer photon detection efficiency (sensitivity) and spatial resolution than PET; however, it has the benefit in some situations of longer radionuclide half-lives, which may better suit the biologic process under examination, as well as the ability to perform multitracer studies using pulse height spectroscopy to separate different radiolabels.
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              Body surface area and body weight predict total liver volume in Western adults.

              Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = -794.41 + 1,267.28 x BSA (square meters; r(2) = 0.46; P <.0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 x weight (kilograms; r(2) = 0.49; P <.0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.
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                Author and article information

                Contributors
                r.bastiaannet@umcutrecht.nl
                skappadath@mdanderson.org
                b.kunnen@umcutrecht.nl
                a.j.a.t.braat@umcutrecht.nl
                m.lam@umcutrecht.nl
                h.w.a.m.dejong@umcutrecht.nl
                Journal
                EJNMMI Phys
                EJNMMI Phys
                EJNMMI Physics
                Springer International Publishing (Cham )
                2197-7364
                2 November 2018
                2 November 2018
                December 2018
                : 5
                : 22
                Affiliations
                [1 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Radiology and Nuclear Medicine, , University Medical Center Utrecht, ; Room E01.132, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
                [2 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Imaging Physics, , The University of Texas MD Anderson Cancer Center, ; 1155 Pressler St, Unit 1352, Houston, TX 77030 USA
                Author information
                http://orcid.org/0000-0001-7056-3229
                Article
                221
                10.1186/s40658-018-0221-z
                6212377
                30386924
                fd04333f-d3b7-464f-91f1-d2292c24feca
                © The Author(s). 2018

                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.

                History
                : 27 November 2017
                : 19 June 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004340, Siemens USA;
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                radioembolization,personalized medicine,dosimetry,radiobiological model,dose-effect relationship,theranostics

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