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      NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy

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          Abstract

          Introduction

          In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography ( 18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients.

          Methods

          Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUV max in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose.

          Results

          Reduction in SUV max was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUV max 17.7, 95% CI 25.8 to − 9.4, p = 0.0001). Of the three lesions with increased SUV max post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy.

          Conclusion

          18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases.

          Trial registration

          POPSTAR, ‘Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy’, Universal Trial Number U1111-1140-7563, Registered 17th April 2013.

          Electronic supplementary material

          The online version of this article (10.1186/s13014-019-1359-0) contains supplementary material, which is available to authorized users.

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          Most cited references20

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          International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery.

          Brett W Cox, Daniel E. Spratt, Michael Lovelock … (2012)
          Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery. Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines. Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space. This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial

            Shankar Siva, Mathias Bressel, Declan G M Murphy … (2018)
            Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available.
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              The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT.

              I Leibovitch, Ur Metser, Gennady Lievshitz … (2006)
              The aim of this study was to compare the detection of bone metastases by 99mTc-methylene diphosphonate (99mTc-MDP) planar bone scintigraphy (BS), SPECT, 18F-Fluoride PET, and 18F-Fluoride PET/CT in patients with high-risk prostate cancer. In a prospective study, BS and 18F-Fluoride PET/CT were performed on the same day in 44 patients with high-risk prostate cancer. In 20 of the latter patients planar BS was followed by single field-of-view (FOV) SPECT and in 24 patients by multi-FOV SPECT of the axial skeleton. Lesions were interpreted separately on each of the 4 modalities as normal, benign, equivocal, or malignant. In patient-based analysis, 23 patients had skeletal metastatic spread (52%) and 21 did not. Categorizing equivocal and malignant interpretation as suggestive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value of planar BS were 70%, 57%, 64%, and 55%, respectively, of multi-FOV SPECT were 92%, 82%, 86%, and 90%, of (18)F-Fluoride PET were 100%, 62%, 74%, and 100%, and of 18F-Fluoride PET/CT were 100% for all parameters. Using the McNemar test, 18F-Fluoride PET/CT was statistically more sensitive and more specific than planar or SPECT BS (P < 0.05) and more specific than 18F-Fluoride PET (P < 0.001). SPECT was statistically more sensitive and more specific than planar BS (P < 0.05) but was less sensitive than 18F-Fluoride PET (P < 0.05). In lesion-based analysis, 156 lesions with increased uptake of 18F-Fluoride were assessed. Based on the corresponding appearance on CT, lesions were categorized by PET/CT as benign (n = 99), osteoblastic metastasis (n = 46), or equivocal when CT was normal (n = 11). Of the 156 18F-Fluoride lesions, 81 lesions (52%), including 34 metastases, were overlooked with normal appearance on planar BS. SPECT identified 62% of the lesions overlooked by planar BS. 18F-Fluoride PET/CT was more sensitive and more specific than BS (P < 0.001) and more specific than PET alone (P < 0.001). 18F-Fluoride PET/CT is a highly sensitive and specific modality for detection of bone metastases in patients with high-risk prostate cancer. It is more specific than 18F-Fluoride PET alone and more sensitive and specific than planar and SPECT BS. Detection of bone metastases is improved by SPECT compared with planar BS and by 18F-Fluoride PET compared with SPECT. This added value of 18F-Fluoride PET/CT may beneficially impact the clinical management of patients with high-risk prostate cancer.
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                Author and article information

                Contributors
                Nicholas Hardcastle:
                ORCID: http://orcid.org/0000-0001-7796-8472
                +61 3 8559 6940 , nick.hardcastle@petermac.org
                Michael S. Hofman: michael.hofman@petermac.org
                Ching-Yu Lee: chingyulee.g@gmail.com
                Jason Callahan: jason.callahan@petermac.org
                Lisa Selbie: lisa.selbie@petermac.org
                Farshad Foroudi: farshad.foroudi@austin.org.au
                Mark Shaw: mark.shaw@petermac.org
                Sarat Chander: sarat.chander@petermac.org
                Andrew Lim: andrew.lim@petermac.org
                Brent Chesson: brent.chesson@petermac.org
                Declan G. Murphy: declan.murphy@petermac.org
                Tomas Kron: tomas.kron@petermac.org
                Shankar Siva: Shankar.siva@petermac.org
                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): 5 September 2019
                Publication date PMC-release: 5 September 2019
                Publication date Collection: 2019
                Volume: 14
                Electronic Location Identifier: 164
                Affiliations
                [1 ]ISNI 0000000403978434, GRID grid.1055.1, Department of Physical Sciences, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [2 ]ISNI 0000000403978434, GRID grid.1055.1, Division of Cancer Imaging, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [3 ]ISNI 0000000403978434, GRID grid.1055.1, Division of Radiation Oncology, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [4 ]Olivia Newton-John Cancer & Wellness Centre | Austin Health, 145 Studley Road, PO Box 5555, Heidelberg, 3084 Australia
                [5 ]ISNI 0000000403978434, GRID grid.1055.1, Department of Radiation Therapy, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [6 ]ISNI 0000000403978434, GRID grid.1055.1, Cancer Surgery, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia
                [7 ]ISNI 0000 0004 0486 528X, GRID grid.1007.6, Centre for Medical Radiation Physics, , University of Wollongong, ; Wollongong, NSW 2522 Australia
                [8 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Sir Peter MacCallum Department of Oncology, , University of Melbourne, ; Parkville, VIC 3000 Australia
                Author information
                http://orcid.org/0000-0001-7796-8472
                Article
                Publisher ID: 1359
                DOI: 10.1186/s13014-019-1359-0
                PMC ID: 6728984
                PubMed ID: 31488175
                SO-VID: 8ea81cda-0295-47f3-b19c-71f8710d1281
                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 : 17 April 2019
                Date accepted : 16 August 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008719, Movember Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000927, Prostate Cancer Foundation of Australia;
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prostate cancer,metastases,sabr,imaging,pet,naf
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prostate cancer, metastases, sabr, imaging, pet, naf

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