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      Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres

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          Abstract

          Background

          Coincidence imaging of low-abundance yttrium-90 ( 90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry.

          Methods

          Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET.

          Results

          Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D 70 > 100 Gy ( D 70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D 70 < 100 Gy; smaller tumors (<80 cm 3) achieved D 70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D 70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D 70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy ( V 20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%).

          Conclusions

          Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

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          Most cited references31

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          Use of normal tissue complication probability models in the clinic.

          The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included. Copyright 2010 Elsevier Inc. All rights reserved.
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            Radiation dose-volume effects in the stomach and small bowel.

            Published data suggest that the risk of moderately severe (>or=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity. Copyright 2010 Elsevier Inc. All rights reserved.
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              Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: radiobiologic considerations.

              Radioactive (90)Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normal-tissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of (99m)Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the (90)Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the >or=grade 2 (G2), >or=grade 3 (G3), and >or=grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the >or=G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n = 1. The radiobiologic approach, based on patient-specific dosimetry, could improve the (90)Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.
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                Author and article information

                Contributors
                Journal
                EJNMMI Res
                EJNMMI Res
                EJNMMI Research
                Springer
                2191-219X
                2013
                25 July 2013
                : 3
                : 57
                Affiliations
                [1 ]Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore 169608, Singapore
                [2 ]Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Hospital Ave, Perth, Western Australia 6009, Australia
                [3 ]Department of Nuclear Medicine, Austin Hospital, Level 1, Harold Stokes Building, 145 Studley Rd, Heidelberg, Melbourne, Victoria 3084, Australia
                [4 ]Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, Helios Building, Singapore 138667, Singapore
                [5 ]Agency for Science, Technology and Research (A*STAR) - National University of Singapore, Centre for Life Sciences, National University of Singapore (NUS) Clinical Imaging Research Centre, 14 Medical Drive, Singapore 117599, Singapore
                [6 ]Centre for Applied Statistics, University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia
                [7 ]Department of Research, Sir Charles Gairdner Hospital, Hospital Ave, Perth, Western Australia 6009, Australia
                [8 ]Department of Radiation Oncology, National University Cancer Institute Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228, Singapore
                [9 ]Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore
                [10 ]Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore
                [11 ]Department of Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
                [12 ]Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, 8 College Rd, Singapore 169857, Singapore
                [13 ]School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia
                [14 ]Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
                Article
                2191-219X-3-57
                10.1186/2191-219X-3-57
                3733999
                23885971
                b0c0e586-654d-4adc-906b-63acf96fecc4
                Copyright ©2013 Kao et al.; licensee Springer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 June 2013
                : 16 July 2013
                Categories
                Original Research

                Radiology & Imaging
                yttrium-90 radioembolization,selective internal radiation therapy,pet/ct,voxel dosimetry,dose-volume histogram,predictive dosimetry

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