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Elshimy Y, Alkhatib AR, Atassi B, Mohammad KS. Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications. Biomedicines 2025; 13:1160. [PMID: 40426987 PMCID: PMC12109438 DOI: 10.3390/biomedicines13051160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/04/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular focus on their implications for bone metastases associated with breast, prostate, lung, and other cancers. A central component of this review is the categorization of pathological biomarkers into four types: diagnostic, prognostic, predictive, and monitoring. We provide a comprehensive evaluation of circulating tumor cells (CTCs), bone turnover markers (such as TRACP-5b and CTX), advanced imaging biomarkers (including PET/CT and MRI), and novel genomic signatures. These biomarkers offer valuable insights for early detection, enhanced risk stratification, and optimized therapeutic decision-making. Furthermore, emerging strategies in immunotherapy and bone-targeted treatments are discussed, highlighting the potential of biomarker-guided precision medicine to enhance personalized patient care. The distinctiveness of this review lies in its integrative approach, combining fundamental pathophysiological insights with the latest developments in biomarker discovery and therapeutic innovation. By synthesizing evidence across various cancer types and biomarker categories, we provide a cohesive framework aimed at advancing both the scientific understanding and clinical management of bone metastases.
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Affiliation(s)
| | | | | | - Khalid S. Mohammad
- Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (Y.E.); (A.R.A.); (B.A.)
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Li L, Chen L, Yang J, Peng D, Xu T, Chen Y. Comparison of 18F-FDG and 68Ga-DOTA-IBA in detecting bone metastases: a lesion-basis study. Sci Rep 2025; 15:12766. [PMID: 40229521 PMCID: PMC11997131 DOI: 10.1038/s41598-025-97920-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 04/08/2025] [Indexed: 04/16/2025] Open
Abstract
Gallium 68 (68Ga)-labeled DOTA-conjugate ibandronic acid (DOTA-IBA) has been successfully synthesized and utilized for bone metastasis imaging. This study compares the diagnostic efficacy between 68Ga-DOTA-IBA and fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) in detecting bone metastases. This prospective study, conducted from October 2022 to September 2023, analyzed images from participants who underwent 68Ga-DOTA-IBA PET/CT and 18F-FDG PET/CT scans. Lesions were classified into five groups based on anatomical location (limbs, vertebrae, pelvis, ribs, and skull). Morphological bone changes were categorized as osteolytic, osteoblastic, or mixed. The semi-quantified radiotracer uptake, measured by the maximum standardized uptake value (SUVmax), was compared using a paired t-test. Detection rates between the two scans were analyzed using the McNemar test. A total of 46 participants (median age: 64 years [interquartile range: 53-68 years], 28 men) were evaluated. 68Ga-DOTA-IBA demonstrated higher diagnostic efficacy than 18F-FDG in detecting bone metastases in the limbs (73.2% vs. 64.1%), vertebras (78.1% vs. 67.4%), ribs (86.6% vs. 62.2%), pelvis (78.6% vs. 68.9%), and skulls (80.0% vs. 38%). For osteoblastic lesions, the detection rate for 68Ga-DOTA-IBA and 18F-FDG was 83.3% and 51.5% respectively (P < 0.001). The SUVmax of 68Ga-DOTA-IBA was 7.88 (95% CI 7.09-8.66), which was higher than that of 18F-FDG at 3.96 (95% CI 3.57-4.35) (P < 0.001). In participants with prostate cancer, the detection rate of 68Ga-DOTA-IBA and 18F-FDG was 84.7% and 55.0% respectively (P < 0.001). The SUVmax of 68Ga-DOTA-IBA was 10.44 (95% CI 8.57-12.30), which was higher than that of 18F-FDG 4.29 (95% CI 3.51-5.07) (P < 0.001). 68Ga-DOTA-IBA PET/CT demonstrates superior diagnostic performance over 18F-FDG PET/CT in detecting bone metastases, particularly in osteoblastic lesions and prostate cancer cases.
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Affiliation(s)
- Linwei Li
- Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China
- Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Lingzhi Chen
- Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China
| | - Jian Yang
- Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China
- Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Dengsai Peng
- Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China
- Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Tingting Xu
- Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China
- Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Yue Chen
- Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No 25 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, China.
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China.
- Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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Gerke O, Naghavi-Behzad M, Nygaard ST, Sigaroudi VR, Vogsen M, Vach W, Hildebrandt MG. Diagnosing Bone Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis on Diagnostic Test Accuracy Studies of 2-[ 18F]FDG-PET/CT, 18F-NaF-PET/CT, MRI, Contrast-Enhanced CT, and Bone Scintigraphy. Semin Nucl Med 2025; 55:137-151. [PMID: 39547916 DOI: 10.1053/j.semnuclmed.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 11/17/2024]
Abstract
This systematic review and network meta-analysis aimed to compare the diagnostic accuracy of 2-[18F]FDG-PET/CT, 18F-NaF-PET/CT, MRI, contrast-enhanced CT, and bone scintigraphy for diagnosing bone metastases in patients with breast cancer. Following PRISMA-DTA guidelines, we reviewed studies assessing 2-[18F]FDG-PET/CT, 18F-NaF-PET/CT, MRI, contrast-enhanced CT, and bone scintigraphy for diagnosing bone metastases in high-stage primary breast cancer (stage III or IV) or known primary breast cancer with suspicion of recurrence (staging or re-staging). A comprehensive search of MEDLINE/PubMed, Scopus, and Embase was conducted until February 2024. Inclusion criteria were original studies using these imaging methods, excluding those focused on AI/machine learning, primary breast cancer without metastases, mixed cancer types, preclinical studies, and lesion-based accuracy. Preference was given to studies using biopsy or follow-up as the reference standard. Risk of bias was assessed using QUADAS-2. Screening, bias assessment, and data extraction were independently performed by two researchers, with discrepancies resolved by a third. We applied bivariate random-effects models in meta-analysis and network meta-analyzed differences in sensitivity and specificity between the modalities. Forty studies were included, with 29 contributing to the meta-analyses. Of these, 13 studies investigated one single modality only. Both 2-[18F]FDG-PET/CT (sensitivity: 0.94, 95% CI: 0.89-0.97; specificity: 0.98, 95% CI: 0.96-0.99), MRI (0.94, 0.82-0.98; 0.93, 0.87-0.96), and 18F-NaF-PET/CT (0.95, 0.85-0.98; 1, 0.93-1) outperformed the less sensitive modalities CE-CT (0.70, 0.62-0.77; 0.98, 0.97-0.99) and bone scintigraphy (0.83, 0.75-0.88; 0.96, 0.87-0.99). The network meta-analysis of multi-modality studies supports the comparable performance of 2-[18F]FDG-PET/CT and MRI in diagnosing bone metastases (estimated differences in sensitivity and specificity, respectively: 0.01, -0.16 - 0.18; -0.02, -0.15 - 0.12). The results from bivariate random effects modelling and network meta-analysis were consistent for all modalities apart from 18F-NaF-PET/CT. We concluded that 2-[18F]FDG-PET/CT and MRI have high and comparable accuracy for diagnosing bone metastases in breast cancer patients. Both outperformed CE-CT and bone scintigraphy regarding sensitivity. Future multimodality studies based on consented thresholds are warranted for further exploration, especially in terms of the potential role of 18F-NaF-PET/CT in bone metastasis diagnosis in breast cancer.
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Affiliation(s)
- Oke Gerke
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
| | - Mohammad Naghavi-Behzad
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark
| | - Sofie Tind Nygaard
- Department of Nuclear Medicine, Aalborg University Hospital, Aalborg, Denmark
| | | | - Marianne Vogsen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Werner Vach
- Basel Academy for Quality and Research in Medicine, Basel, Switzerland
| | - Malene Grubbe Hildebrandt
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark; Centre for Innovative Medical Technology, Odense University Hospital, Odense, Denmark
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Katal S, McKay MJ, Taubman K. PET Molecular Imaging in Breast Cancer: Current Applications and Future Perspectives. J Clin Med 2024; 13:3459. [PMID: 38929989 PMCID: PMC11205053 DOI: 10.3390/jcm13123459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Positron emission tomography (PET) plays a crucial role in breast cancer management. This review addresses the role of PET imaging in breast cancer care. We focus primarily on the utility of 18F-fluorodeoxyglucose (FDG) PET in staging, recurrence detection, and treatment response evaluation. Furthermore, we delve into the growing interest in precision therapy and the development of novel radiopharmaceuticals targeting tumor biology. This includes discussing the potential of PET/MRI and artificial intelligence in breast cancer imaging, offering insights into improved diagnostic accuracy and personalized treatment approaches.
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Affiliation(s)
- Sanaz Katal
- Medical Imaging Department, St. Vincent’s Hospital Melbourne, Fitzroy, VIC 3065, Australia;
| | - Michael J. McKay
- Northwest Regional Hospital, University of Tasmania, Burnie, TAS 7320, Australia;
- Northern Cancer Service, Northwest Regional Hospital, Burnie, TAS 7320, Australia
| | - Kim Taubman
- Medical Imaging Department, St. Vincent’s Hospital Melbourne, Fitzroy, VIC 3065, Australia;
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Guo X, Zhou N, Liu J, Ding J, Liu T, Song G, Zhu H, Yang Z. Comparison of an Affibody-based Molecular Probe and 18F-FDG for Detecting HER2-Positive Breast Cancer at PET/CT. Radiology 2024; 311:e232209. [PMID: 38888484 DOI: 10.1148/radiol.232209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2024]
Abstract
Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose To compare an affibody-based tracer, Al18F-NOTA-HER2-BCH, and fluorine 18 (18F) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUVmax) and target to background ratio (TBR) and compared using a general linear mixed model. Results A total of 42 participants (mean age, 56.3 years ± 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with Al18F-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with 18F-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with Al18F-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with 18F-FDG. Al18F-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than 18F-FDG. The SUVmax and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on Al18F-NOTA-HER2-BCH images than on 18F-FDG images (median SUVmax range, 10.4-13.5 vs 3.4-6.2; P value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; P value range, <.001 to .001). No evidence of differences in the SUVmax and TBR for chest wall or lung metastases was observed between Al18F-NOTA-HER2-BCH and 18F-FDG (P value range, .06 to .53). Conclusion PET/CT with the affibody-based tracer Al18F-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using 18F-FDG. ClinicalTrials.gov Identifier: NCT04547309 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ulaner in this issue.
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Affiliation(s)
- Xiaoyi Guo
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Nina Zhou
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jiayue Liu
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jin Ding
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Teli Liu
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Guohong Song
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Hua Zhu
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhi Yang
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine (X.G., N.Z., J.L., J.D., T.L., H.Z., Z.Y.), and Department of Breast Oncology (G.S.), Peking University Cancer Hospital & Institute, Beijing 100142, China
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Robson N, Thekkinkattil DK. Current Role and Future Prospects of Positron Emission Tomography (PET)/Computed Tomography (CT) in the Management of Breast Cancer. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:321. [PMID: 38399608 PMCID: PMC10889944 DOI: 10.3390/medicina60020321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 02/07/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024]
Abstract
Breast cancer has become the most diagnosed cancer in women globally, with 2.3 million new diagnoses each year. Accurate early staging is essential for improving survival rates with metastatic spread from loco regional to distant metastasis, decreasing mortality rates by 50%. Current guidelines do not advice the routine use of positron emission tomography (PET)-computed tomography (CT) in the staging of early breast cancer in the absence of symptoms. However, there is a growing body of evidence to suggest that the use of PET-CT in this early stage can benefit the patient by improving staging and as a result treatment and outcomes, as well as psychological burden, without increasing costs to the health service. Ongoing research in PET radiomics and artificial intelligence is showing promising future prospects in its use in diagnosis, staging, prognostication, and assessment of responses to the treatment of breast cancer. Furthermore, ongoing research to address current limitations of PET-CT by improving techniques and tracers is encouraging. In this narrative review, we aim to evaluate the current evidence of the usefulness of PET-CT in the management of breast cancer in different settings along with its future prospects, including the use of artificial intelligence (AI), radiomics, and novel tracers.
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Affiliation(s)
- Nicole Robson
- Lincoln Medical School, Ross Lucas Medical Sciences Building, University of Lincoln, Lincoln LN6 7FS, UK;
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Ouvrard E, Kaseb A, Poterszman N, Porot C, Somme F, Imperiale A. Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine? Front Med (Lausanne) 2024; 10:1320574. [PMID: 38288299 PMCID: PMC10823373 DOI: 10.3389/fmed.2023.1320574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/28/2023] [Indexed: 01/31/2024] Open
Abstract
Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.
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Affiliation(s)
- Eric Ouvrard
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Ashjan Kaseb
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
- Radiology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Nathan Poterszman
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Clémence Porot
- Radiopharmacy, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France
| | - Francois Somme
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Alessio Imperiale
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
- IPHC, UMR 7178, CNRS/Unistra, Strasbourg, France
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Xia L, Lai J, Huang D, Qiu S, Hu H, Luo Y, Cao J. Comparing the diagnostic efficacy of [ 18F]FDG PET/CT and [ 18F]FDG PET/MRI for detecting bone metastases in breast cancer: a meta-analysis. Radiol Oncol 2023; 57:299-309. [PMID: 37494596 PMCID: PMC10561067 DOI: 10.2478/raon-2023-0037] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 06/15/2023] [Indexed: 07/28/2023] Open
Abstract
BACKGROUND This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]FDG PET/CT and [18F] FDG PET/MRI in detecting bone metastases in breast cancer patients. METHODS An extensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases to identify available publications up to February 2023. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET/CT and [18F]FDG PET/MRI in patients with breast cancer bone metastases. Sensitivity and specificity were assessed using the DerSimonian and Laird method, followed by transformation via the Freeman-Tukey double inverse sine transformation. RESULTS 16 articles (including 4 head-to-head comparison articles) involving 1,261 patients were included in the meta-analysis. The overall sensitivity of [18F]FDG PET/CT in patient-based analysis, lesion-based analysis, and head-to-head comparison were 0.73, 0.89, and 0.87, respectively, while the overall sensitivity of [18F]FDG PET/MRI were 0.99, 0.99, and 0.99. The results indicated that [18F]FDG PET/MRI appears to a higher sensitivity in comparison to [18F]FDG PET/CT(all P < 0.05). In contrast, the overall specificity of [18F]FDG PET/CT in patient-based analysis, lesion-based analysis, and head-to-head comparison were 1.00, 0.99, and 1.00, respectively, while the overall specificity of [18F]FDG PET/MRI were 1.00, 0.99, and 0.98. These results suggested that [18F]FDG PET/CT has a similar level of specificity compared to [18F]FDG PET/MRI. CONCLUSIONS Our meta-analysis indicates that [18F]FDG PET/MRI demonstrates superior sensitivity and similar specificity to [18F]FDG PET/CT in detecting bone metastases in breast cancer patients. Further prospective research is required to confirm these findings and assess the clinical application of these techniques.
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Affiliation(s)
- Longjie Xia
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
| | - Jianqin Lai
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
| | - Di Huang
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
| | - Shenghui Qiu
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
| | - Huiqiong Hu
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
- Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yunxiang Luo
- Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jie Cao
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People's Hospital, Guangzhou, Guangzhou, China
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Hao Y, Zhang F, Ma Y, Luo Y, Zhang Y, Yang N, Liu M, Liu H, Li J. Potential biomarkers for the early detection of bone metastases. Front Oncol 2023; 13:1188357. [PMID: 37404755 PMCID: PMC10315674 DOI: 10.3389/fonc.2023.1188357] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 06/01/2023] [Indexed: 07/06/2023] Open
Abstract
The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient's quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases.
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Affiliation(s)
- Yang Hao
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
- Henan University of Chinese Medicine, Zhengzhou, China
| | - Feifan Zhang
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
- Hunan University of Chinese Medicine, Changsha, China
| | - Yan Ma
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
| | - Yage Luo
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
| | - Yongyong Zhang
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
| | - Ning Yang
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
| | - Man Liu
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
| | - Hongjian Liu
- Department of Orthopaedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jitian Li
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China
- Henan University of Chinese Medicine, Zhengzhou, China
- Hunan University of Chinese Medicine, Changsha, China
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10
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Edelmuth DGL, Helito PVP, Filippi RZ, Baptista AM, Bordalo M. Staging of primary and secondary solid musculoskeletal tumors. Skeletal Radiol 2023; 52:365-378. [PMID: 35974195 DOI: 10.1007/s00256-022-04118-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 02/02/2023]
Affiliation(s)
- Diogo Guilherme Leão Edelmuth
- Radiology Department, Instituto de Ortopedia E Traumatologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.,Radiology Department, Instituto de Radiologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Paulo Victor Partezani Helito
- Radiology Department, Instituto de Ortopedia E Traumatologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.,Radiology Department, Instituto de Radiologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Renée Zon Filippi
- Pathology Department, Instituto de Ortopedia E Traumatologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - André Mathias Baptista
- Orthopedic Oncology Department, Instituto de Ortopedia E Traumatologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Marcelo Bordalo
- Radiology Department, Instituto de Ortopedia E Traumatologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. .,Radiology Department, Instituto de Radiologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
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11
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Hadebe B, Harry L, Ebrahim T, Pillay V, Vorster M. The Role of PET/CT in Breast Cancer. Diagnostics (Basel) 2023; 13:diagnostics13040597. [PMID: 36832085 PMCID: PMC9955497 DOI: 10.3390/diagnostics13040597] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/05/2023] [Accepted: 01/16/2023] [Indexed: 02/08/2023] Open
Abstract
Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases (11.7%), followed by lung cancer (11.4%) The current literature and the National Comprehensive Cancer Network (NCCN) guidelines state that 18F-FDG PET/CT is not routine for early diagnosis of breast cancer, and rather PET/CT scanning should be performed for patients with stage III disease or when conventional staging studies yield non-diagnostic or suspicious results because this modality has been shown to upstage patients compared to conventional imaging and thus has an impact on disease management and prognosis. Furthermore, with the growing interest in precision therapy in breast cancer, numerous novel radiopharmaceuticals have been developed that target tumor biology and have the potential to non-invasively guide the most appropriate targeted therapy. This review discusses the role of 18F-FDG PET and other PET tracers beyond FDG in breast cancer imaging.
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Affiliation(s)
- Bawinile Hadebe
- Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa
- Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa
- Correspondence:
| | - Lerwine Harry
- Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa
- Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa
| | - Tasmeera Ebrahim
- Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa
- Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa
| | - Venesen Pillay
- Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa
- Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa
| | - Mariza Vorster
- Department of Nuclear Medicine, College of Health Sciences, University of KwaZulu Natal, Private Bag X54001, Durban 4001, South Africa
- Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa
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12
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Suto H, Inui Y, Okamura A. Is CT or FDG-PET more useful for evaluation of the treatment response in metastatic HER2-positive breast cancer? a case report and literature review. Front Oncol 2023; 13:1158797. [PMID: 37152012 PMCID: PMC10157226 DOI: 10.3389/fonc.2023.1158797] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 04/05/2023] [Indexed: 05/09/2023] Open
Abstract
Response evaluation criteria in solid tumors version 1.1 (RECIST ver1.1) has been widely adopted to evaluate treatment efficacy in solid tumors, including breast cancer (BC), in clinical trials and clinical practice. RECIST is based mainly on computed tomography (CT) images, and the role of fluorodeoxyglucose-positron emission tomography (FDG-PET) is limited. However, because the rate of tumor shrinkage on CT does not necessarily reflect the potential remaining tumor cells, there may be a discrepancy between the treatment response and prognosis in some cases. Here we report a case of metastatic human epidermal growth factor receptor 2 (HER2)-positive BC where FDG-PET was preferable to CT for evaluation of the treatment response. A 40-year-old woman became aware of a lump in her right breast in September 201X. She was pregnant and underwent further examinations, including a biopsy, in November. The diagnosis was HER2-positive BC (cT2N2bM1, stage IV). Trastuzumab plus pertuzumab plus docetaxel (TPD) therapy was initiated in December 201X. CT performed in February 201X+1 showed cystic changes in the metastatic lesions in the liver, and the treatment response was stable disease (SD) according to RECIST. However, FDG-PET in March 201X+1 did not detect abnormal uptake of FDG in the hepatic lesions. The disease remained stable thereafter. Thus, tumor shrinkage may not be apparent in situations where the response to treatment results in rapid changes in blood flow within the tumor, which is associated with cystic changes. When patients with hypervascular liver metastases receive treatment with highly effective regimens, the target lesion may show cystic changes rather than shrinkage, as observed in the present case. Therefore, FDG-PET is sometimes superior to CT in judging a tumor response.
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Affiliation(s)
- Hirotaka Suto
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
- *Correspondence: Hirotaka Suto,
| | - Yumiko Inui
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Atsuo Okamura
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
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13
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Vijayakumar S, Yang J, Nittala MR, Velazquez AE, Huddleston BL, Rugnath NA, Adari N, Yajurvedi AK, Komanduri A, Yang CC, Duggar WN, Berlin WP, Duszak R, Vijayakumar V. Changing Role of PET/CT in Cancer Care With a Focus on Radiotherapy. Cureus 2022; 14:e32840. [PMID: 36694538 PMCID: PMC9867792 DOI: 10.7759/cureus.32840] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2022] [Indexed: 12/24/2022] Open
Abstract
Positron emission tomography (PET) integrated with computed tomography (CT) has brought revolutionary changes in improving cancer care (CC) for patients. These include improved detection of previously unrecognizable disease, ability to identify oligometastatic status enabling more aggressive treatment strategies when the disease burden is lower, its use in better defining treatment targets in radiotherapy (RT), ability to monitor treatment responses early and thus improve the ability for early interventions of non-responding tumors, and as a prognosticating tool as well as outcome predicting tool. PET/CT has enabled the emergence of new concepts such as radiobiotherapy (RBT), radioimmunotherapy, theranostics, and pharmaco-radiotherapy. This is a rapidly evolving field, and this primer is to help summarize the current status and to give an impetus to developing new ideas, clinical trials, and CC outcome improvements.
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Affiliation(s)
| | - Johnny Yang
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - Mary R Nittala
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | | | | | - Nickhil A Rugnath
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - Neha Adari
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - Abhay K Yajurvedi
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - Abhinav Komanduri
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - Claus Chunli Yang
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - William N Duggar
- Radiation Oncology, University of Mississippi Medical Center, Jackson, USA
| | - William P Berlin
- Radiology, University of Mississippi Medical Center, Jackson, USA
| | - Richard Duszak
- Radiology, University of Mississippi Medical Center, Jackson, USA
| | - Vani Vijayakumar
- Radiology, University of Mississippi Medical Center, Jackson, USA
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14
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Corines MJ, Coffey K, Dou E, Lobaugh S, Zheng J, Hwang S, Feigin K. Bone Lesions Detected on Breast MRI: Clinical Outcomes and Features Associated with Metastatic Breast Cancer. JOURNAL OF BREAST IMAGING 2022; 4:600-611. [PMID: 37744182 PMCID: PMC10516530 DOI: 10.1093/jbi/wbac053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Objective To determine prevalence and frequency of malignancy among bone lesions detected on breast MRI and to identify clinical and imaging features associated with bone metastases from breast cancer (BC), as bone lesions are suboptimally evaluated on breast imaging protocols and can present a diagnostic challenge. Methods This IRB-approved retrospective review of breast MRIs performed from June 2009 to June 2018 identified patients with bone lesions. Demographic, clinical, and MRI features were reviewed. Clinical outcome of bone lesions was determined based on pathology and/or additional diagnostic imaging. All benign lesions had ≥ 2 years of imaging follow-up. Statistics were computed with Fisher's exact and Wilcoxon rank sum tests. Results Among all patients with breast MRI, 1.2% (340/29 461) had bone lesions. Of these, 224 were confirmed benign or metastatic BC by pathology or imaging follow-up, with 70.1% (157/224) be- nign and 29.9% (67/224) metastatic. Bone metastases were associated with BC history (P < 0.001), with metastases occurring in 58.2% (53/91) of patients with current BC, 17.9% (14/78) patients with prior BC, and 0.0% (0/55) without BC. Bone metastases were associated with invasive and ad- vanced stage BC and, on MRI, with location in sternum, ribs, or clavicles, larger size, multiplicity, andT1 hypointensity (all P < 0.01 in tests of overall association). Conclusion Of clinically confirmed breast MRI-detected bone lesions, 30% were bone metastases; all were detected in patients with current or prior BC. Metastases were associated with advanced stage, invasive carcinoma, larger lesion size, multiplicity, low T1 signal, and non-spine location.
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Affiliation(s)
- Marina J. Corines
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY, USA
| | - Kristen Coffey
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY, USA
| | - Eda Dou
- University of California San Francisco, Department of Radiology and Biomedical Imagery, San Francisco, CA, USA
| | - Stephanie Lobaugh
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Junting Zheng
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sinchun Hwang
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY, USA
| | - Kimberly Feigin
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY, USA
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15
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Cook GJR. Imaging of Bone Metastases in Breast Cancer. Semin Nucl Med 2022; 52:531-541. [PMID: 35236615 PMCID: PMC7616189 DOI: 10.1053/j.semnuclmed.2022.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 11/11/2022]
Abstract
Bone metastases are a common site of spread in advanced breast cancer and responsible for morbidity and high health care costs. Imaging contributes to staging and response assessment of the skeleton and has been instrumental in guiding patient management for several decades. Historically this has been with radiographs, computed tomography and bone scans. More recently, molecular and hybrid imaging methods have undergone significant development, including the addition of single photon emission computed tomography/computed tomography to the bone scan, positron emission tomography, with bone-specific and tumor-specific tracers, and magnetic resonance imaging with complementary functional diffusion-weighted imaging. These have allowed different aspects of the abnormal biology associated with bone metastases to be explored. There is ability to interrogate the bone microenvironment with bone-specific tracers and cancer cell characteristics with tumor-specific methods that complement morphological appearances on computed tomography or magnetic resonance imaging. Alongside the advent of novel, more effective and nuanced therapies for bone metastases in breast cancer, there is accumulating evidence that the developments in imaging allow more sensitive and specific detection of bone metastases as well as more accurate and earlier assessment of treatment response leading to improvements in patient management.
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Affiliation(s)
- Gary J R Cook
- Cancer Imaging Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK; King's College London & Guy's and St Thomas' PET Centre, St Thomas' Hospital, London, UK.
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16
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Grunbaum A, Kremer R. Parathyroid hormone-related protein (PTHrP) and malignancy. VITAMINS AND HORMONES 2022; 120:133-177. [PMID: 35953108 DOI: 10.1016/bs.vh.2022.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
PTHrP (parathyroid hormone related protein) is an important mediator of malignancy-related tumor progression and hypercalcemia that shares considerable homology and functionality with parathyroid hormone. In this chapter, we review what has been elucidated to date regarding PTHrP's role in malignancies. Starting with a review of calcium metabolism and regulation, we then summarize the discovery and structure of PTHrP and development of sensitive immunoassays for specific measurement. Subsequently, we explore its role in tumor progression, with emphasis on the primary tumor as well as skeletal and non-osseus metastases. We then consider the clinical implications of PTHrP in cancer before concluding with a discussion of both established and potential treatments for malignancy associated hypercalcemia and bone metastases.
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Affiliation(s)
- Ami Grunbaum
- Calcium Research Laboratories and Department of Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada
| | - Richard Kremer
- Calcium Research Laboratories and Department of Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada.
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17
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Edmonds CE, O'Brien SR, Mankoff DA, Pantel AR. Novel applications of molecular imaging to guide breast cancer therapy. Cancer Imaging 2022; 22:31. [PMID: 35729608 PMCID: PMC9210593 DOI: 10.1186/s40644-022-00468-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 05/30/2022] [Indexed: 11/10/2022] Open
Abstract
The goals of precision oncology are to provide targeted drug therapy based on each individual’s specific tumor biology, and to enable the prediction and early assessment of treatment response to allow treatment modification when necessary. Thus, precision oncology aims to maximize treatment success while minimizing the side effects of inadequate or suboptimal therapies. Molecular imaging, through noninvasive assessment of clinically relevant tumor biomarkers across the entire disease burden, has the potential to revolutionize clinical oncology, including breast oncology. In this article, we review breast cancer positron emission tomography (PET) imaging biomarkers for providing early response assessment and predicting treatment outcomes. For 2-18fluoro-2-deoxy-D-glucose (FDG), a marker of cellular glucose metabolism that is well established for staging multiple types of malignancies including breast cancer, we highlight novel applications for early response assessment. We then review current and future applications of novel PET biomarkers for imaging the steroid receptors, including the estrogen and progesterone receptors, the HER2 receptor, cellular proliferation, and amino acid metabolism.
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Affiliation(s)
- Christine E Edmonds
- Department of Radiology, Hospital of the University if Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
| | - Sophia R O'Brien
- Department of Radiology, Hospital of the University if Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - David A Mankoff
- Department of Radiology, Hospital of the University if Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - Austin R Pantel
- Department of Radiology, Hospital of the University if Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
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18
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Bhaludin BN, Tunariu N, Senthivel N, Babiker A, Soneji ND, Hujairi N, Sharma B, McGrath SE, Okines AF, Ring AE, Messiou C, Downey K, Koh DM. Does the addition of whole-body MRI to routine imaging influence real-world treatment decisions in metastatic breast cancer? Cancer Imaging 2022; 22:26. [PMID: 35672838 PMCID: PMC9172188 DOI: 10.1186/s40644-022-00464-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 05/26/2022] [Indexed: 11/26/2022] Open
Abstract
Background The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC. Methods MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated. Results There were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone. 81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%). 24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone. SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC). Conclusions The use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further.
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Affiliation(s)
- Basrull N Bhaludin
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK.
| | - Nina Tunariu
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK.,Institute of Cancer Research, London, England, UK
| | - Nishanthi Senthivel
- Department of Medicine - Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK
| | - Amna Babiker
- Department of Medicine - Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK
| | - Neil D Soneji
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK.,Department of Radiology and Nuclear Medicine, Imperial College Healthcare NHS Trust, Fulham Palace Rd, London, W6 8RF, England, UK
| | - Nabil Hujairi
- Department of Nuclear Medicine, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK
| | - Bhupinder Sharma
- Department of Radiology and Nuclear Medicine, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK
| | - Sophie E McGrath
- Department of Medicine - Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK
| | - Alicia F Okines
- Department of Medicine - Breast Unit, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK
| | - Alistair E Ring
- Department of Medicine - Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK
| | - Christina Messiou
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK.,Institute of Cancer Research, London, England, UK
| | - Kate Downey
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, England, UK
| | - Dow-Mu Koh
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, SM2 5PT, England, UK.,Institute of Cancer Research, London, England, UK
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19
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Bhaludin BN, Tunariu N, Koh DM, Messiou C, Okines AF, McGrath SE, Ring AE, Parton MM, Sharma B, Gagliardi T, Allen SD, Pope R, Johnston SRD, Downey K. A review on the added value of whole-body MRI in metastatic lobular breast cancer. Eur Radiol 2022; 32:6514-6525. [PMID: 35384456 DOI: 10.1007/s00330-022-08714-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 03/02/2022] [Accepted: 03/04/2022] [Indexed: 12/01/2022]
Abstract
Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.
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Affiliation(s)
- Basrull N Bhaludin
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK.
| | - Nina Tunariu
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, England, SM2 5PT, UK.,Institute of Cancer Research, London, UK
| | - Dow-Mu Koh
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, England, SM2 5PT, UK.,Institute of Cancer Research, London, UK
| | - Christina Messiou
- Department of Radiology, The Royal Marsden Hospital, Downs Rd, Sutton, England, SM2 5PT, UK.,Institute of Cancer Research, London, UK
| | - Alicia F Okines
- Breast Unit, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Sophie E McGrath
- Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, England, SM2 5PT, UK
| | - Alistair E Ring
- Breast Unit, The Royal Marsden Hospital, Downs Rd, Sutton, England, SM2 5PT, UK
| | - Marina M Parton
- Breast Unit, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Bhupinder Sharma
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Tanja Gagliardi
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Steven D Allen
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Romney Pope
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Stephen R D Johnston
- Breast Unit, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
| | - Kate Downey
- Department of Radiology, The Royal Marsden Hospital, 203 Fulham Rd, London, England, SW3 6JJ, UK
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Imaging of Oligometastatic Disease. Cancers (Basel) 2022; 14:cancers14061427. [PMID: 35326586 PMCID: PMC8946296 DOI: 10.3390/cancers14061427] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 11/22/2022] Open
Abstract
Simple Summary The imaging of oligometastatic disease (OMD) is challenging as it requires precise loco-regional staging and whole-body assessment. The combination of imaging modalities is often required. The more accurate imaging tool will be selected according to tumor type, the timing with regard to measurement and treatment, metastatic location, and the patient’s individual risk for metastasis. The most commonly used modalities are contrast-enhanced computed tomography (CT), magnetic resonance imaging and metabolic and receptor-specific imaging, particularly, 18F-fluorodesoxyglucose positron emission tomography/CT, used alone or in combination. Abstract Oligometastatic disease (OMD) is an emerging state of disease with limited metastatic tumor burden. It should be distinguished from polymetastatic disease due the potential curative therapeutic options of OMD. Imaging plays a pivotal role in the diagnosis and follow-up of patients with OMD. The imaging tools needed in the case of OMD will differ according to different parameters, which include primary tumor type, timing between measurement and treatment, potential metastatic location and the patient’s individual risk for metastasis. In this article, OMD is defined and the use of different imaging modalities in several oncologic situations are described in order to better understand OMD and its specific implication for radiologists.
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21
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Lee L, Kazmer A, Colman MW, Gitelis S, Batus M, Blank AT. What is the clinical impact of staging and surveillance PET-CT scan findings in patients with bone and soft tissue sarcoma? J Surg Oncol 2022; 125:901-906. [PMID: 35023167 DOI: 10.1002/jso.26789] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/15/2021] [Accepted: 01/02/2022] [Indexed: 01/23/2023]
Abstract
BACKGROUND AND OBJECTIVES Positron emission tomography-computerized tomography (PET-CTs) are becoming increasingly utilized in sarcoma care, workup, and surveillance. This study aimed to describe additional PET-CT findings as well as subsequent workups and changes in the clinical course due to those results. METHODS Patient records were retrospectively reviewed, and the additional workups and evaluations triggered by PET-CT findings were qualitatively analyzed to document their results. Additional changes in the clinical course were documented. RESULTS A total of 183 bone and soft tissue sarcoma patients underwent PET-CT as part of staging or surveillance. Additional workup was performed in 31.5% (n = 41 of 130) patients who had positive PET-CT findings. Among these, 36.6% (n = 15 of 41) patients had clinically significant findings that altered the clinical course. Overall, 14.8% (n = 27 of 183) experienced a change in the clinical course due to PET-CT. CONCLUSION PET-CT often highlights lesions of potential clinical importance. Additional workup, as well as changes in the clinical course, were not infrequent. Future, multi-institutional studies should address the value of PET-CT in sarcoma care.
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Affiliation(s)
- Linus Lee
- Department of Orthopedic Surgery, Division of Orthopedic Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Alexander Kazmer
- Department of Orthopedic Surgery, Division of Orthopedic Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Matthew W Colman
- Department of Orthopedic Surgery, Division of Orthopedic Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Steven Gitelis
- Department of Orthopedic Surgery, Division of Orthopedic Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Marta Batus
- Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, Chicago, Illinois, USA
| | - Alan T Blank
- Department of Orthopedic Surgery, Division of Orthopedic Oncology, Rush University Medical Center, Chicago, Illinois, USA
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22
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Shi XQ, Zhang H, Liu X, Dong Y, Yang P, Qian L. Feasibility and efficiency of contrast enhanced ultrasound real time guided fine needle aspiration for sentinel lymph node of breast cancer. Clin Hemorheol Microcirc 2022; 80:267-279. [PMID: 34719485 DOI: 10.3233/ch-211226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM To assess the feasibility and efficiency of contrast-enhanced ultrasound (CEUS) real-time guided fine needle aspiration (FNA) for sentinel lymph node (SLN) of breast cancer. MATERIALS AND METHODS This retrospective study reviewed 21 breast cancer patients who scheduled for surgical resection performed CEUS real-time guided SLN-FNA and intraoperative SLN biopsy (SLNB). The success rate of CEUS real-time guided SLN-FNA was analyzed. The FNA diagnostic efficiency of SLN metastasis was analyzed compared to SLNB. RESULTS Twenty-six SLNs were detected by intradermal CEUS whereas 130 SLNs were detected by SLNB. The median SLNs detected by intradermal CEUS (n = 1) and by SLNB (n = 5) was significantly difference (p < 0.001). All 26 CE-SLNs of 21 patients were successfully performed intradermal CEUS dual image real-time guided SLN-FNA including 5 SLNs of 4 patients which were difficult to distinguish in conventional ultrasound. Compared to SLNB, FNA found 2 of 5 cases of SLN metastasis, the diagnosis sensitivity, specificity, positive predictive value, negative predictive value, false negative rate, false positive rate and Yoden index were 40%, 100%, 100%, 84.2%, 60%, 0%and 40%, respectively. CONCLUSION SLN-FNA real-time guided by dual CEUS image mode was technically feasible. Patients with a positive SLN-FNA should be advised to ALND without intraoperative SLNB according to Chinese surgeon and patients' conservatism attitude. But a negative SLN-FNA did not obviate the need of conventional SLNB because of the high false negative rate.
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Affiliation(s)
- Xian-Quan Shi
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Huiming Zhang
- Department of Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xi Liu
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yunyun Dong
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Peipei Yang
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Linxue Qian
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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23
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Oprea-Lager DE, Cysouw MC, Boellaard R, Deroose CM, de Geus-Oei LF, Lopci E, Bidaut L, Herrmann K, Fournier LS, Bäuerle T, deSouza NM, Lecouvet FE. Bone Metastases Are Measurable: The Role of Whole-Body MRI and Positron Emission Tomography. Front Oncol 2021; 11:772530. [PMID: 34869009 PMCID: PMC8640187 DOI: 10.3389/fonc.2021.772530] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 11/04/2021] [Indexed: 12/14/2022] Open
Abstract
Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone lesions, which can change in morphology due to treatment effects and/or secondary bone remodeling. Hence, morphological imaging is regarded unsuitable for response assessment of bone metastases and in the current Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) guideline bone metastases are deemed unmeasurable. Nevertheless, the advent of functional and molecular imaging modalities such as whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography (PET) has improved the ability for follow-up of bone metastases, regardless of their morphology. Both these modalities not only have improved sensitivity for visual detection of bone lesions, but also allow for objective measurements of bone lesion characteristics. WB-MRI provides a global assessment of skeletal metastases and for a one-step "all-organ" approach of metastatic disease. Novel MRI techniques include diffusion-weighted imaging (DWI) targeting highly cellular lesions, dynamic contrast-enhanced MRI (DCE-MRI) for quantitative assessment of bone lesion vascularization, and multiparametric MRI (mpMRI) combining anatomical and functional sequences. Recommendations for a homogenization of MRI image acquisitions and generalizable response criteria have been developed. For PET, many metabolic and molecular radiotracers are available, some targeting tumor characteristics not confined to cancer type (e.g. 18F-FDG) while other targeted radiotracers target specific molecular characteristics, such as prostate specific membrane antigen (PSMA) ligands for prostate cancer. Supporting data on quantitative PET analysis regarding repeatability, reproducibility, and harmonization of PET/CT system performance is available. Bone metastases detected on PET and MRI can be quantitatively assessed using validated methodologies, both on a whole-body and individual lesion basis. Both have the advantage of covering not only bone lesions but visceral and nodal lesions as well. Hybrid imaging, combining PET with MRI, may provide complementary parameters on the morphologic, functional, metabolic and molecular level of bone metastases in one examination. For clinical implementation of measuring bone metastases in response assessment using WB-MRI and PET, current RECIST1.1 guidelines need to be adapted. This review summarizes available data and insights into imaging of bone metastases using MRI and PET.
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Affiliation(s)
- Daniela E. Oprea-Lager
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Matthijs C.F. Cysouw
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Ronald Boellaard
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Christophe M. Deroose
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
- Nuclear Medicine & Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
- Biomedical Photonic Imaging Group, University of Twente, Enschede, Netherlands
| | - Egesta Lopci
- Nuclear Medicine Unit, IRCCS – Humanitas Research Hospital, Milan, Italy
| | - Luc Bidaut
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- College of Science, University of Lincoln, Lincoln, United Kingdom
| | - Ken Herrmann
- Department of Nuclear Medicine, University of Duisburg-Essen, and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Laure S. Fournier
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- Paris Cardiovascular Research Center (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Radiology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Hopital europeen Georges Pompidou, Université de Paris, Paris, France
- European Imaging Biomarkers Alliance (EIBALL), European Society of Radiology, Vienna, Austria
| | - Tobias Bäuerle
- Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Nandita M. deSouza
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- European Imaging Biomarkers Alliance (EIBALL), European Society of Radiology, Vienna, Austria
- Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Frederic E. Lecouvet
- Imaging Group, European Organisation of Research and Treatment in Cancer (EORTC), Brussels, Belgium
- Department of Radiology, Institut de Recherche Expérimentale et Clinique (IREC), Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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Hansen JA, Naghavi-Behzad M, Gerke O, Baun C, Falch K, Duvnjak S, Alavi A, Høilund-Carlsen PF, Hildebrandt MG. Diagnosis of bone metastases in breast cancer: Lesion-based sensitivity of dual-time-point FDG-PET/CT compared to low-dose CT and bone scintigraphy. PLoS One 2021; 16:e0260066. [PMID: 34793550 PMCID: PMC8601566 DOI: 10.1371/journal.pone.0260066] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 11/02/2021] [Indexed: 11/18/2022] Open
Abstract
We compared lesion-based sensitivity of dual-time-point FDG-PET/CT, bone scintigraphy (BS), and low-dose CT (LDCT) for detection of various types of bone metastases in patients with metastatic breast cancer. Prospectively, we included 18 patients with recurrent breast cancer who underwent dual-time-point FDG-PET/CT with LDCT and BS within a median time interval of three days. A total of 488 bone lesions were detected on any of the modalities and were categorized by the LDCT into osteolytic, osteosclerotic, mixed morphologic, and CT-negative lesions. Lesion-based sensitivity was 98.2% (95.4-99.3) and 98.8% (96.8-99.5) for early and delayed FDG-PET/CT, respectively, compared with 79.9% (51.1-93.8) for LDCT, 76.0% (36.3-94.6) for BS, and 98.6% (95.4-99.6) for the combined BS+LDCT. BS detected only 51.2% of osteolytic lesions which was significantly lower than other metastatic types. SUVs were significantly higher for all lesion types on delayed scans than on early scans (P<0.0001). Osteolytic and mixed-type lesions had higher SUVs than osteosclerotic and CT-negative metastases at both time-points. FDG-PET/CT had significantly higher lesion-based sensitivity than LDCT and BS, while a combination of the two yielded sensitivity comparable to that of FDG-PET/CT. Therefore, FDG-PET/CT could be considered as a sensitive one-stop-shop in case of clinical suspicion of bone metastases in breast cancer patients.
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Affiliation(s)
- Jeanette Ansholm Hansen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark
| | - Mohammad Naghavi-Behzad
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- * E-mail:
| | - Oke Gerke
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Christina Baun
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Kirsten Falch
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sandra Duvnjak
- Radiology Department–Breast Imaging, Herlev Gentofte Hospital, Copenhagen, Denmark
- Mammography Screening Center in the Capital Region, Herlev Gentofte Hospital, Copenhagen, Denmark
| | - Abass Alavi
- Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States of America
| | - Poul Flemming Høilund-Carlsen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Malene Grubbe Hildebrandt
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- Centre for Innovative Medical Technology, Odense University Hospital, Odense, Denmark
- Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark
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25
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Price J. The sternum: An important review area when reporting pre-surgical staging breast MRI studies. J Med Imaging Radiat Oncol 2021; 66:404-408. [PMID: 34725929 DOI: 10.1111/1754-9485.13344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/17/2021] [Indexed: 11/26/2022]
Abstract
Identification and assessment of extramammary findings on contrast-enhanced breast MRI scans is particularly important in the setting of newly diagnosed invasive cancer as metastatic lesions may be encountered in the liver, lungs, pleural cavity or bones. Establishing that stage IV disease is present has a profound effect on patient management. The sternum is routinely included on breast MRI studies and can be an early site for breast cancer metastases. These appear as enhancing lesions with high signal on fat-suppressed T2-weighted images. However, incidental benign lesions, notably haemangiomas, may also be encountered, and careful analysis is required to avoid false-positive results. Clinical context is important with a much lower likelihood of malignancy in the setting of routine screening of young women with no personal history of breast cancer. This pictorial essay illustrates findings encountered with lesions in the sternum and offers insights into how to interpret and manage them.
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Affiliation(s)
- Jeremy Price
- Qscan Radiology Clinics, Canberra, Australian Capital Territory, Australia
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26
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Moon JB, Yoo SW, Lee C, Kim DY, Pyo A, Kwon SY. Multimodal Imaging-Based Potential Visualization of the Tumor Microenvironment in Bone Metastasis. Cells 2021; 10:cells10112877. [PMID: 34831100 PMCID: PMC8616082 DOI: 10.3390/cells10112877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/11/2021] [Accepted: 10/22/2021] [Indexed: 11/16/2022] Open
Abstract
Bone metastasis (BM) is the most common malignant bone tumor and a significant cause of morbidity and mortality for patients with cancer. Compared to other metastatic organs, bone has unique characteristics in terms of the tumor microenvironment (TME). Precise assessments of the TME in BM could be an important step for developing an optimized management plan for patient care. Imaging approaches for BM have several advantages, such as biopsy not being required, multiple site evaluation, and serial assessment in the same sites. Owing to the developments of new imaging tracers or imaging modalities, bone TME could be visualized using multimodal imaging techniques. In this review, we describe the BM pathophysiology, diagnostic principles of major imaging modalities, and clinically available imaging modalities to visualize the TME in BM. We also discuss how the interactions between various factors affecting the TME could be visualized using multimodal imaging techniques.
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Affiliation(s)
- Jang Bae Moon
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun 58128, Korea; (J.B.M.); (S.W.Y.); (C.L.)
| | - Su Woong Yoo
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun 58128, Korea; (J.B.M.); (S.W.Y.); (C.L.)
| | - Changho Lee
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun 58128, Korea; (J.B.M.); (S.W.Y.); (C.L.)
| | - Dong-Yeon Kim
- College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju 52828, Korea;
| | - Ayoung Pyo
- Accelerator & RI Development Team, Korea Atomic Energy Research Institute, Daejeon 56212, Korea;
| | - Seong Young Kwon
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun 58128, Korea; (J.B.M.); (S.W.Y.); (C.L.)
- Correspondence: ; Tel.: +82-61-379-7273
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27
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Heath CL, Esserman LJ, Flavell RR, Melisko ME. Authors' Reply: To the Letter to the Editor by Groheux et al. J Natl Compr Canc Netw 2021; 19:xxx-xxxii. [PMID: 34416710 DOI: 10.6004/jnccn.2021.7080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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28
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Han S, Choi JY. Impact of 18F-FDG PET, PET/CT, and PET/MRI on Staging and Management as an Initial Staging Modality in Breast Cancer: A Systematic Review and Meta-analysis. Clin Nucl Med 2021; 46:271-282. [PMID: 33651022 PMCID: PMC7938917 DOI: 10.1097/rlu.0000000000003502] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 11/28/2020] [Accepted: 11/28/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVES We performed a systematic review and meta-analysis to evaluate the impact of 18F-FDG PET, PET/CT, and PET/MRI on staging and management during the initial staging of breast cancer. METHODS We searched the PubMed, Embase, Cochrane Library, and KoreaMed databases until March 2020 to identify studies that reported the proportion of breast cancer patients whose clinical stage or management were changed after PET scans. The proportion of changes was pooled using a random-effects model. Subgroup and metaregression analyses were performed to explore heterogeneity. RESULTS We included 29 studies (4276 patients). The pooled proportions of changes in stage and management were 25% (95% confidence interval [CI], 21%-30%) and 18% (95% CI, 14%-23%), respectively. When stage changes were stratified according to initial stage, the pooled proportions were 11% (95% CI, 3%-22%) in stage I, 20% (95% CI, 16%-24%) in stage II, and 34% (95% CI, 27%-42%) in stage III. The relative proportions of intermodality and intention-to-treat changes were 74% and 70%, respectively. Using metaregression analyses, the mean age and the proportion of initial stage III to IV and histologic grade II to III were significant factors affecting the heterogeneity in changes in stage or management. CONCLUSIONS Currently available literature suggests that the use of 18F-FDG PET, PET/CT, or PET/MRI leads to significant modification of staging and treatment in newly diagnosed breast cancer patients. Therefore, there may be a role for routine clinical use of PET imaging for the initial staging of breast cancer.
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Affiliation(s)
- Sangwon Han
- From the Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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29
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Mohd Rohani MF, Zanial AZ, Suppiah S, Phay Phay K, Mohamed Aslum Khan F, Mohamad Najib FH, Mohd Noor N, Arumugam M, Amir Hassan SZ, Vinjamuri S. Bone single-photon emission computed tomography/computed tomography in cancer care in the past decade: a systematic review and meta-analysis as well as recommendations for further work. Nucl Med Commun 2021; 42:9-20. [PMID: 33165258 DOI: 10.1097/mnm.0000000000001306] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Skeletal whole-body scintigraphy (WBS), although widely used as a sensitive tool for detecting metastatic bone disease in oncology cases, has relatively low specificity. Indeterminate bone lesions (IBLs) detected by WBS cause a diagnostic dilemma, which hampers further management plans. In the advent of hybrid imaging, single-photon emission computed tomography/computed tomography (SPECT/CT) has been gaining popularity as a tool to improve the characterisation of IBLs detected by WBS. As yet, there has not been a systematic review to objectively evaluate the diagnostic capabilities of SPECT/CT in this area. We conducted a systematic review of relevant electronic databases up to 30 August 2020. The outcomes of interest were the reporting of SPECT/CT to identify benign and malignant IBLs and the calculation of the sensitivity and specificity of the index test, based on histopathological examination or clinical and imaging follow-up as the reference standard. After the risk of bias and eligibility assessment, 12 articles were identified and synthesised in the meta-analysis. The pooled sensitivity and specificity of SPECT/CT for diagnosing IBLs are 93.0% [95% confidence interval (CI) 0.91-0.95] and 96.0% (95% CI 0.94-0.97), respectively. There was heterogeneity of the articles due to variable imaging protocols, duration of follow-up and scoring methods for interpreting the SPECT/CT results. The heterogeneity poses a challenge for accurate interpretation of the true diagnostic capability of SPECT/CT. In conclusion, targeted SPECT/CT improves the specificity of diagnosing bone metastases, but efforts need to be made to standardise the thresholds for SPECT/CT, methodology, as well as harmonising the reporting and interpretation criteria. We also make some recommendations for future works.
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Affiliation(s)
| | | | - Subapriya Suppiah
- Department of Nuclear Medicine, Hospital Kuala Lumpur
- Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
| | | | | | | | - Noramaliza Mohd Noor
- Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
| | - Manohar Arumugam
- Department of Orthopaedic, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia
| | | | - Sobhan Vinjamuri
- Department of Nuclear Medicine, The Royal Liverpool and Broadgreen University Hospitals, NHS Trust, Liverpool, UK
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30
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Diagnostic performance of whole-body SPECT/CT in bone metastasis detection using 99mTc-labelled diphosphate: a systematic review and meta-analysis. Clin Radiol 2020; 75:961.e11-961.e24. [DOI: 10.1016/j.crad.2020.07.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 07/09/2020] [Indexed: 11/17/2022]
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31
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Li H, Ye T, Li N, Xia G, Li B, Zhang Y, Hu H, Sun Y, Zhang Y, Xiang J, Ma D, Weng Y, Liu S, Jia C, Qian B, Gu Y, Li Y, Song S, Chen H. Is 99m Tc bone scintigraphy necessary in the preoperative workup for patients with cT1N0 subsolid lung cancer? A prospective multicenter cohort study. Thorac Cancer 2020; 12:415-419. [PMID: 33210466 PMCID: PMC7882389 DOI: 10.1111/1759-7714.13752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/01/2020] [Accepted: 11/01/2020] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND 99m Tc bone scintigraphy (BS) is still the most common approach for the evaluation of bone metastasis in China. The purpose of this study was to investigate the necessity of BS as part of a routine preoperative workup for patients with cT1N0 subsolid lung cancer. METHODS This was a prospective multicenter clinical trial (NCT03689439). Patients with cT1N0 subsolid nodules who were candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The surgical plan could be changed if a positive result was detected. The primary endpoint was the incidence rate of the surgical plan being changed because of positive BS results. The secondary endpoint was the rate of positive BS findings and the rate of related complications. RESULTS From November 2018 to July 2019, 691 patients were enrolled into the study. None of the patients had positive BS results and no surgical plans were changed by BS findings. There were 222 male and 469 female patients. The average age was 54.8 ± 3.7 years old. The average tumor diameter was 14.9 ± 4.2 mm. There were 282 patients with pure GGO nodules and 409 with part-solid nodules. A total of 470 patients had a single nodule, while 221 patients had multifocal lesions. The number of patients whose pathological diagnosis was invasive adenocarcinoma, minimally invasive adenocarcinoma, adenocarcinoma in situ and mucinous adenocarcinoma was 357, 293, 32 and nine, respectively. The number of patients who underwent lobectomy, segmentectomy and wedge resection was 234, 199 and 258, respectively. CONCLUSIONS 99m Tc bone scintigraphy is unnecessary in the preoperative workup for patients with cT1N0 subsolid lung cancer. KEY POINTS SIGNIFICANT FINDINGS OF THE STUDY: In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings. WHAT THIS STUDY ADDS We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients. Clinical trial registry number: NCT03689439.
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Affiliation(s)
- Hang Li
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ting Ye
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Nan Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Guozhan Xia
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Bin Li
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yang Zhang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Hu
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yihua Sun
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yawei Zhang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiaqing Xiang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dongchun Ma
- Department of Thoracic Surgery, Anhui Chest Hospital, Hefei, China
| | - Yuan Weng
- Department of Thoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Shilei Liu
- Department of Thoracic Surgery, Henan Cancer Hospital, Zhengzhou, China
| | - Chunyi Jia
- Department of Thoracic Surgery, Jilin Cancer Hospital, Changchun, China
| | - Bin Qian
- Department of Thoracic Surgery, Jiang Du People's Hospital, Jiangdu, China
| | - Yajia Gu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yuan Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shaoli Song
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Haiquan Chen
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Gillman JA, Pantel AR, Mankoff DA, Edmonds CE. Update on Quantitative Imaging for Predicting and Assessing Response in Oncology. Semin Nucl Med 2020; 50:505-517. [PMID: 33059820 PMCID: PMC9788668 DOI: 10.1053/j.semnuclmed.2020.07.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Molecular imaging has revolutionized clinical oncology by imaging-specific facets of cancer biology. Through noninvasive measurements of tumor physiology, targeted radiotracers can serve as biomarkers for disease characterization, prognosis, response assessment, and predicting long-term response/survival. In turn, these imaging biomarkers can be utilized to tailor therapeutic regimens to tumor biology. In this article, we review biomarker applications for response assessment and predicting long-term outcomes. 18F-fluorodeoxyglucose (FDG), a measure of cellular glucose metabolism, is discussed in the context of lymphoma and breast and lung cancer. FDG has gained widespread clinical acceptance and has been integrated into the routine clinical care of several malignancies, most notably lymphoma. The novel radiotracers 16α-18F-fluoro-17β-estradiol and 18F-fluorothymidine are reviewed in application to the early prediction of response assessment of breast cancer. Through illustrative examples, we explore current and future applications of molecular imaging biomarkers in the advancement of precision medicine.
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Affiliation(s)
- Jennifer A Gillman
- Department of Radiology, Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Austin R Pantel
- Department of Radiology, Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - David A Mankoff
- Department of Radiology, Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Christine E Edmonds
- Department of Radiology, Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
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van Es SC, Velleman T, Elias SG, Bensch F, Brouwers AH, Glaudemans AWJM, Kwee TC, Iersel MWV, Maduro JH, Oosting SF, de Vries EGE, Schröder CP. Assessment of Bone Lesions with 18F-FDG PET Compared with 99mTc Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management. J Nucl Med 2020; 62:177-183. [PMID: 32817140 DOI: 10.2967/jnumed.120.244640] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 05/07/2020] [Indexed: 11/16/2022] Open
Abstract
It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by 18F-FDG PET instead of 99mTc bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by 18F-FDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and 18F-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either 18F-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 102 evaluated patients (39% by ceCT, 26% by BS, and 87% by 18F-FDG PET). Additional bone lesions on 18F-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with 18F-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional 18F-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, 18F-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for 18F-FDG PET. On the basis of these data, 18F-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC.
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Affiliation(s)
- Suzanne C van Es
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ton Velleman
- Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Sjoerd G Elias
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Frederike Bensch
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Adrienne H Brouwers
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
| | - Andor W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
| | - Thomas C Kwee
- Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Marleen Woltman-van Iersel
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - John H Maduro
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Sjoukje F Oosting
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Elisabeth G E de Vries
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Carolina P Schröder
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Akaike G, Akaike T, Fadl SA, Lachance K, Nghiem P, Behnia F. Imaging of Merkel Cell Carcinoma: What Imaging Experts Should Know. Radiographics 2020; 39:2069-2084. [PMID: 31697628 DOI: 10.1148/rg.2019190102] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor with a higher mortality rate than melanoma. Approximately 40% of MCC patients have nodal or distant metastasis at initial presentation, and one-third of patients will develop distant metastatic disease over their clinical course. Although MCC is rare, its incidence has been steadily increasing. Furthermore, the immunogenicity of MCC and its diagnostic and therapeutic application have made MCC one of the most rapidly developing topics in dermatology and oncology. Owing to the aggressive and complex nature of MCC, a multidisciplinary approach is necessary for management of this tumor, including dermatologists, surgeons, radiation oncologists, medical oncologists, pathologists, radiologists, and nuclear medicine physicians. Imaging plays a crucial role in diagnosis, planning for surgery or radiation therapy, and assessment of treatment response and surveillance. However, MCC is still not well recognized among radiologists and nuclear medicine physicians, likely owing to its rarity. The purpose of this review is to raise awareness of MCC among imaging experts by describing the epidemiology, pathophysiology, and clinical features of MCC and current clinical management with a focus on the role of imaging. The authors highlight imaging findings characteristic of MCC, as well as the clinical significance of CT, MRI, sentinel lymph node mapping, fluorine 18 fluorodeoxyglucose PET/CT, and other nuclear medicine studies such as bone scintigraphy and somatostatin receptor scintigraphy. ©RSNA, 2019.
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Affiliation(s)
- Gensuke Akaike
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
| | - Tomoko Akaike
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
| | - Shaimaa A Fadl
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
| | - Kristina Lachance
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
| | - Paul Nghiem
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
| | - Fatemeh Behnia
- From the Division of Nuclear Medicine, Department of Radiology (G.A., F.B.), and Division of Dermatology, Department of Medicine (T.A., K.L., P.N.), University of Washington, 1959 NE Pacific St, Box 356113, Seattle, WA 98195-6113; and Department of Radiology, Virginia Commonwealth University Health System, Richmond, Va (S.A.F.)
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Boers J, de Vries EFJ, Glaudemans AWJM, Hospers GAP, Schröder CP. Application of PET Tracers in Molecular Imaging for Breast Cancer. Curr Oncol Rep 2020; 22:85. [PMID: 32627087 PMCID: PMC7335757 DOI: 10.1007/s11912-020-00940-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Molecular imaging with positron emission tomography (PET) is a powerful tool to visualize breast cancer characteristics. Nonetheless, implementation of PET imaging into cancer care is challenging, and essential steps have been outlined in the international "imaging biomarker roadmap." In this review, we identify hurdles and provide recommendations for implementation of PET biomarkers in breast cancer care, focusing on the PET tracers 2-[18F]-fluoro-2-deoxyglucose ([18F]-FDG), sodium [18F]-fluoride ([18F]-NaF), 16α-[18F]-fluoroestradiol ([18F]-FES), and [89Zr]-trastuzumab. RECENT FINDINGS Technical validity of [18F]-FDG, [18F]-NaF, and [18F]-FES is established and supported by international guidelines. However, support for clinical validity and utility is still pending for these PET tracers in breast cancer, due to variable endpoints and procedures in clinical studies. Assessment of clinical validity and utility is essential towards implementation; however, these steps are still lacking for PET biomarkers in breast cancer. This could be solved by adding PET biomarkers to randomized trials, development of imaging data warehouses, and harmonization of endpoints and procedures.
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Affiliation(s)
- Jorianne Boers
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Erik F J de Vries
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Andor W J M Glaudemans
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Geke A P Hospers
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Carolina P Schröder
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
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Cook GJR, Goh V. Molecular Imaging of Bone Metastases and Their Response to Therapy. J Nucl Med 2020; 61:799-806. [PMID: 32245899 DOI: 10.2967/jnumed.119.234260] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 03/30/2020] [Indexed: 12/18/2022] Open
Abstract
Bone metastases are common, especially in more prevalent malignancies such as breast and prostate cancer. They cause significant morbidity and draw on health-care resources. Molecular and hybrid imaging techniques, including SPECT/CT, PET/CT, and whole-body MRI with diffusion-weighted imaging, have improved diagnostic accuracy in staging the skeleton compared with previous standard imaging methods, allowing earlier tailored treatment. With the introduction of several effective treatment options, it is now even more important to detect and monitor response in bone metastases accurately. Conventional imaging, including radiographs, CT, MRI, and bone scintigraphy, are recognized as being insensitive and nonspecific for response monitoring in a clinically relevant time frame. Early reports of molecular and hybrid imaging techniques, as well as whole-body MRI, promise an earlier and more accurate prediction of response versus nonresponse but have yet to be adopted routinely in clinical practice. We summarize the role of new molecular and hybrid imaging methods, including SPECT/CT, PET/CT, and whole-body MRI. These modalities are associated with improvements in diagnostic accuracy for the staging and response assessment of skeletal metastases over standard imaging methods, being able to quantify biologic processes related to the bone microenvironment as well as tumor cells. The described improvements in the imaging of bone metastases and their response to therapy have led to adoption of some of these methods into routine clinical practice in some centers. These methods also provide a better way to assess the treatment response of bone metastases in clinical trials.
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Affiliation(s)
- Gary J R Cook
- Cancer Imaging Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Vicky Goh
- Cancer Imaging Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
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37
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Edge J, Budge M, Webner A, Doruyter A, Cilliers G, Malherbe F. Metastatic screening for patients with newly diagnosed breast cancer: Who and how? SOUTH AFRICAN JOURNAL OF ONCOLOGY 2020. [DOI: 10.4102/sajo.v4i0.94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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38
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Taralli S, Caldarella C, Lorusso M, Scolozzi V, Altini C, Rubini G, Calcagni ML. Comparison between 18F-FDG and 18F-NaF PET imaging for assessing bone metastases in breast cancer patients: a literature review. Clin Transl Imaging 2020. [DOI: 10.1007/s40336-020-00363-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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39
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Lee AY, Navarro R, Busby LP, Greenwood HI, Bucknor MD, Ray KM, Joe BN. Characterization of Metastatic Sternal Lesions on Dynamic Contrast-Enhanced Breast MRI in Women with Invasive Breast Cancer. Acad Radiol 2019; 26:1358-1362. [PMID: 30527457 DOI: 10.1016/j.acra.2018.11.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Revised: 11/07/2018] [Accepted: 11/17/2018] [Indexed: 12/15/2022]
Abstract
RATIONALE AND OBJECTIVES Detecting sternal lesions is not the purpose of breast MRI, but diagnosing metastasis has major clinical implications. Our purpose was to determine the breast MRI features of sternal metastases detected on PET-CT and bone-scan. MATERIALS AND METHODS Between 01/2010-09/2018, 379 patients with breast cancer had sternal findings on PET-CT or bone-scan, 21 of which underwent breast MRI within 100 days. Sternal lesions were considered metastatic if (1) biopsy demonstrated metastasis, (2) the lesion had similar appearance to synchronous sites of biopsy-proven osseous metastases, or (3) there were numerous suspicious lesions in which widespread osseous metastasis was presumed. Four radiologists reviewed the MR images to determine if metastases were retrospectively detectable. MRI reports were reviewed to determine if lesions were prospectively described. MRI features of metastatic sternal lesions were compared to benign controls. RESULTS Fourteen sternal metastases met inclusion criteria. Lesions were retrospectively detectable on breast MRI by all radiologists in 86% (12/14) of cases, but prospectively reported in 57%. Of the 12 MRI-detectable metastases, mean maximum dimension was 33 mm, 7 had >1 lesion, all were T1-hypointense, 11 were T2-hyperintense, 11 were noncircumscribed, 6 extended beyond cortex, 11 enhanced heterogeneously, and 11 demonstrated washout. Heterogeneous enhancement (p = 0.002), noncircumscribed margins (p < 0.001), multiplicity (p = 0.005), and size >1 cm (p < 0.001) were more frequent with metastatic compared to benign sternal lesions. CONCLUSION Most sternal metastases (86%) were retrospectively detectable on breast MRI, but only 57% were prospectively reported, emphasizing the importance evaluating the sternum on breast MRI. Certain MRI features may raise suspicion for metastasis.
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Paydary K, Seraj SM, Zadeh MZ, Emamzadehfard S, Shamchi SP, Gholami S, Werner TJ, Alavi A. The Evolving Role of FDG-PET/CT in the Diagnosis, Staging, and Treatment of Breast Cancer. Mol Imaging Biol 2019. [PMID: 29516387 DOI: 10.1007/s11307-018-1181-3] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The applications of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer have been extensively studied. According to these studies, PET/CT is not routinely performed for the diagnosis of primary breast cancer, although PET/CT in specific subtypes of breast cancer correlates with histopathologic features of the primary tumor. PET/CT can detect metastases to mediastinal, axial, and internal mammary nodes, but it cannot replace the sentinel node biopsy. In detection of distant metastases, this imaging tool may have a better accuracy in detecting lytic bone metastases compared to bone scintigraphy. Thus, PET/CT is recommended when advanced-stage disease is suspected, and conventional modalities are inconclusive. Also, PET/CT has a high sensitivity and specificity to detect loco-regional recurrence and is recommended in asymptomatic patients with rising tumor markers. Numerous studies support the future role of PET/CT in prediction of response to neoadjuvant chemotherapy (NAC). PET/CT has a higher diagnostic value for prognostic risk stratification in comparison with conventional modalities. With the continuing research on the treatment planning and evaluation of patients with breast cancer, the role of PET/CT can be further extended.
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Affiliation(s)
- Koosha Paydary
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | | | | | | | | | - Saeid Gholami
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Thomas J Werner
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Abass Alavi
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. .,Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
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Inaki A, Nakajima K, Wakabayashi H, Mochizuki T, Kinuya S. Fully automated analysis for bone scintigraphy with artificial neural network: usefulness of bone scan index (BSI) in breast cancer. Ann Nucl Med 2019; 33:755-765. [PMID: 31317398 DOI: 10.1007/s12149-019-01386-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 07/11/2019] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Artificial neural network (ANN) technology has been developed for clinical use to analyze bone scintigraphy with metastatic bone tumors. It has been reported to improve diagnostic accuracy and reproducibility especially in cases of prostate cancer. The aim of this study was to evaluate the diagnostic usefulness of quantitative bone scintigraphy with ANN in patients having breast cancer. PATIENTS AND METHODS We retrospectively evaluated 88 patients having breast cancer who underwent both bone scintigraphy and 18F-fluorodeoxyglucose (FDG) positron-emission computed tomography/X-ray computed tomography (PET/CT) within an interval of 8 weeks between both examinations for comparison. The whole-body bone images were analyzed with fully automated software that was customized according to a Japanese multicenter database. The region of interest for FDG-PET was set to bone lesions in patients with bone metastasis, while the bone marrow of the ilium and the vertebra was used in patients without bone metastasis. RESULTS Thirty of 88 patients had bone metastasis. Extent of disease, bone scan index (BSI) which indicate severity of bone metastasis, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and serum tumor markers in patients with bone metastasis were significantly higher than those in patients without metastasis. The Kaplan-Meier survival curve showed that the overall survival of the lower BSI group was longer than that with the higher BSI group in patients with visceral metastasis. In the multivariate Cox proportional hazard model, BSI (hazard ratio (HR): 19.15, p = 0.0077) and SUVmax (HR: 10.12, p = 0.0068) were prognostic factors in patients without visceral metastasis, while the BSI was only a prognostic factor in patients with visceral metastasis (HR: 7.88, p = 0.0084), when dividing the sample into two groups with each mean value in patients with bone metastasis. CONCLUSION BSI, an easily and automatically calculated parameter, was a well prognostic factor in patients with visceral metastasis as well as without visceral metastasis from breast cancer.
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Affiliation(s)
- Anri Inaki
- Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
| | - Kenichi Nakajima
- Department of Functional Imaging and Artificial Intelligence, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Hiroshi Wakabayashi
- Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Takafumi Mochizuki
- Kanazawa Advanced Medical Center, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Seigo Kinuya
- Department of Nuclear Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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Raynor WY, Al-Zaghal A, Zadeh MZ, Seraj SM, Alavi A. Metastatic Seeding Attacks Bone Marrow, Not Bone: Rectifying Ongoing Misconceptions. PET Clin 2019; 14:135-144. [PMID: 30420215 DOI: 10.1016/j.cpet.2018.08.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Conventional modalities, such as bone scintigraphy, are commonly used to assess osseous abnormalities in skeletal metastasis. Fluorine-18 (18F)-sodium fluoride (NaF) PET similarly portrays osteoblastic activity but with improved spatial and contrast resolution and more accurate anatomic localization. However, these modalities rely on indirect evidence for tumor activity. PET imaging with 18F-fluorodeoxyglucose (FDG) and tumor-specific tracers may have an increased role by directly portraying the metabolic activity of cancer cells, which are often seeded in bone marrow and cause osseous disease after initial latency. This article describes the utility and limitations of these modalities in assessing skeletal metastases.
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Affiliation(s)
- William Y Raynor
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; Department of Radiology, Drexel University College of Medicine, 230 N Broad Street, Philadelphia, PA 19102, USA
| | - Abdullah Al-Zaghal
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - Mahdi Zirakchian Zadeh
- Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Siavash Mehdizadeh Seraj
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - Abass Alavi
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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Abstract
Bone is the most common site of metastasis for breast cancer. Bone metastasis significantly affects both quality of life and survival of the breast cancer patient. Clinically, complications secondary to bone metastasis include pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Because bone metastasis is extremely common in patients with metastatic breast cancer, clinical management of bone metastases is an important and challenging aspect of treatment in the metastatic setting.The skeleton is a metabolically active organ system that undergoes continuous remodeling throughout life. A delicate balance of the bone-forming osteoblasts and bone-resorbing osteoclasts in the dynamic microenvironment of the skeleton maintains normal bone remodeling and integrity. The presence of metastatic lesions in bone disrupts the normal bone microenvironment and upsets the fine balance between the key components. The changes in the bone microenvironment then create a vicious cycle that further promotes bone destruction and tumor progression.Various therapeutic options are available for bone metastases of breast cancer. Treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Commonly used modalities include local therapies such as surgery, radiation therapy and radiofrequency ablation (RFA) together with systemic therapies such as endocrine therapy, chemotherapy, monoclonal antibody-based therapy, bone-enhancing therapy and radioisotope therapy. Despite the use of various therapeutic modalities, bone metastases eventually become resistant to therapy, and disease progresses.In this chapter, we describe the clinical picture and biological mechanism of bone metastases in breast cancer. We also discuss known risk factors as well as detection and assessment of bone metastases. We present therapeutic options for bone metastasis using a multidisciplinary approach. Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies.
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Radionuclide Therapy for Bone Metastases: Utility of Scintigraphy and PET Imaging for Treatment Planning. PET Clin 2018; 13:491-503. [PMID: 30219184 DOI: 10.1016/j.cpet.2018.05.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The skeleton is a common site for cancer metastases. Bone metastases are a major cause of morbidity and mortality and associated with pain, pathologic fractures, spinal cord compression, and decreased survival. Various radionuclides have been used for pain therapy. Recently, an α-emitter has been shown to improve overall survival of patients with bone metastases from castration-resistant prostate cancer and was approved as a therapeutic agent. The aim of this article is to provide an overview regarding state of the art radionuclide therapy options for bone metastases, with focus on the role of PET imaging in therapy planning.
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Cook GJ, Goh V. Functional and Hybrid Imaging of Bone Metastases. J Bone Miner Res 2018; 33:961-972. [PMID: 29665140 PMCID: PMC7616187 DOI: 10.1002/jbmr.3444] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 04/02/2018] [Accepted: 04/06/2018] [Indexed: 12/21/2022]
Abstract
Bone metastases are common, cause significant morbidity, and impact on healthcare resources. Although radiography, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy have frequently been used for staging the skeleton, these methods are insensitive and nonspecific for monitoring treatment response in a clinically relevant time frame. We summarize several recent reports on new functional and hybrid imaging methods including single photon emission CT/CT, positron emission tomography/CT, and whole-body MRI with diffusion-weighted imaging. These modalities generally show improvements in diagnostic accuracy for staging and response assessment over standard imaging methods, with the ability to quantify biological processes related to the bone microenvironment as well as tumor cells. As some of these methods are now being adopted into routine clinical practice and clinical trials, further evaluation with comparative studies is required to guide optimal and cost-effective clinical management of patients with skeletal metastases. © 2018 American Society for Bone and Mineral Research.
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Affiliation(s)
- Gary Jr Cook
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London SE1 7EH, United Kingdom
- King's College London and Guy's & St Thomas' PET Centre, St Thomas' Hospital, London SE1 7EH, United Kingdom
| | - Vicky Goh
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London SE1 7EH, United Kingdom
- Radiology Department, Guy's & St Thomas' Hospitals, London SE1 7EH, United Kingdom
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Caresia Aroztegui AP, García Vicente AM, Alvarez Ruiz S, Delgado Bolton RC, Orcajo Rincon J, Garcia Garzon JR, de Arcocha Torres M, Garcia-Velloso MJ. 18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging. Tumour Biol 2017; 39:1010428317728285. [PMID: 29025377 DOI: 10.1177/1010428317728285] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Current guidelines do not systematically recommend 18F-FDG PET/CT for breast cancer staging; and the recommendations and level of evidence supporting its use in different groups of patients vary among guidelines. This review summarizes the evidence about the role of 18F-FDG PET/CT in breast cancer staging and the therapeutic and prognostic impact accumulated in the last decade. Other related aspects, such as the association of metabolic information with biology and prognosis are considered and evidence-based recommendations for the use of 18F-FDG PET/CT in breast cancer staging are offered. We systematically searched MEDLINE for articles reporting studies with at least 30 patients related to clinical questions following the Problem/Population, Intervention, Comparison, and Outcome framework. We critically reviewed the selected articles and elaborated evidence tables structuring the summarized information into methodology, results, and limitations. The level of evidence and the grades of recommendation for the use of 18F-FDG PET/CT in different contexts are summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial staging in patients with recently diagnosed breast cancer; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak recommendation in this population. In patients with locally advanced breast cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a strong recommendation in this population. In patients with recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG PET/CT is associated with tumor biology and has prognostic implications, supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended for staging all patients with early breast cancer, although evidence of improved regional and systemic staging supports its use in locally advanced breast cancer. Baseline tumor glycolytic activity is associated with tumor biology and prognosis.
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Affiliation(s)
| | - Ana María García Vicente
- 2 Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - Soledad Alvarez Ruiz
- 3 Department of Nuclear Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Roberto Carlos Delgado Bolton
- 4 Department of Diagnostic Imaging and Nuclear Medicine, Hospital San Pedro-Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain
| | - Javier Orcajo Rincon
- 5 Department of Nuclear Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Bone metastases from breast cancer: associations between morphologic CT patterns and glycolytic activity on PET and bone scintigraphy as well as explorative search for influential factors. Ann Nucl Med 2017; 31:719-725. [PMID: 28864931 PMCID: PMC5691120 DOI: 10.1007/s12149-017-1202-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 08/29/2017] [Indexed: 11/28/2022]
Abstract
Background This study aimed to compare the detection of bone metastases from breast cancer on F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy (BS). An explorative search for factors influencing the sensitivity or uptake of BS and FDG-PET was also performed. Methods Eighty-eight patients with bone metastases from breast cancer were eligible for this study. Histological confirmation of bone metastases was obtained in 31 patients. The bone metastases were visually classified into four types based on their computed tomography (CT) appearance: osteoblastic, osteolytic, mixed, and negative. The sensitivity of BS and FDG-PET were obtained regarding CT type, adjuvant therapy, and the primary tumor characteristics. The FDG maximum standardized uptake value (SUVmax) was analyzed. Results The sensitivities of the three modalities (CT, BS, and FDG-PET) were 77, 89, and 94%, respectively. The sensitivity of FDG-PET for the osteoblastic type (69%) was significantly lower than that for the other types (P < 0.001), and the sensitivity of BS for the negative type (70%) was significantly lower than that for the others. Regarding tumor characteristics, the sensitivity of FDG-PET significantly differed between nuclear grade (NG)1 and NG2–3 (P = 0.032). The SUVmax of the osteoblastic type was significantly lower than that of the other types (P = 0.009). The SUVmax of NG1 was also significantly lower than that of NG2–3 (P = 0.011). No significant difference in FDG uptake (SUVmax) was detected between different histological types. Conclusion Although FDG-PET is superior to BS for the detection of bone metastases from breast cancer, this technique has limitations in depicting osteoblastic bone metastases and NG1.
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48
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Piva R, Ticconi F, Ceriani V, Scalorbi F, Fiz F, Capitanio S, Bauckneht M, Cittadini G, Sambuceti G, Morbelli S. Comparative diagnostic accuracy of 18F-FDG PET/CT for breast cancer recurrence. BREAST CANCER-TARGETS AND THERAPY 2017; 9:461-471. [PMID: 28740429 PMCID: PMC5503278 DOI: 10.2147/bctt.s111098] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In the last decades, in addition to conventional imaging techniques and magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has been shown to be relevant in the detection and management of breast cancer recurrence in doubtful cases in selected groups of patients. While there are no conclusive data indicating that imaging tests, including FDG PET/CT, produce a survival benefit in asymptomatic patients, FDG PET/CT can be useful for identifying the site of relapse when traditional imaging methods are equivocal or conflicting and for identifying or confirming isolated loco-regional relapse or isolated metastatic lesions. The present narrative review deals with the potential role of FDG PET in these clinical settings by comparing its accuracy and impact with conventional imaging modalities such as CT, ultrasound, bone scan, 18F-sodium fluoride PET/CT (18F-NaF PET/CT) as well as MRI. Patient-focused perspectives in terms of patients' satisfaction and acceptability are also discussed.
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Affiliation(s)
- Roberta Piva
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | - Flavia Ticconi
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | - Valentina Ceriani
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | - Federica Scalorbi
- Nuclear Medicine Unit, S. Orsola-Malpighi University Hospital, Bologna
| | - Francesco Fiz
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | | | - Matteo Bauckneht
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | | | - Gianmario Sambuceti
- Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa
| | - Silvia Morbelli
- Nuclear Medicine Unit, IRCCS AOU San Martino - IST, Genoa, Italy
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SEOM Clinical Guideline for bone metastases from solid tumours (2016). Clin Transl Oncol 2016; 18:1243-1253. [PMID: 27896639 PMCID: PMC5138247 DOI: 10.1007/s12094-016-1590-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 11/18/2016] [Indexed: 12/25/2022]
Abstract
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
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Ahmed F, Muzaffar R, Fernandes H, Tu Y, Albalooshi B, Osman MM. Skeletal Metastasis as Detected by 18F-FDG PET with Negative CT of the PET/CT: Frequency and Impact on Cancer Staging and/or Management. Front Oncol 2016; 6:208. [PMID: 27777898 PMCID: PMC5056322 DOI: 10.3389/fonc.2016.00208] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 09/13/2016] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVES The aim of our study is to assess the frequency of detection of PET-positive computed tomography (CT)-negative skeletal metastases (SM) and determine the impact of such detection on staging and/or management in patients who had FDG PET/CT as part of the cancer work-up. METHODS We retrospectively reviewed 2000 18F-FDG PET/CT scans of known cancer patients. A log was kept to record cases of suspected SM with or without bone changes from the low-dose non-contrast CT. The presence or absence of SM was evaluated based on available pathological and clinical data. The impact of detection of such lesions on cancer staging and/or management was evaluated by a board certified oncologist. RESULTS Of the 2000 cases, 18F-FDG PET/CT suggested SM in 146/2000 (7.3%). Of those 146 cases, 105 (72%) were positive on both PET and CT. The remaining 41 (28%) had PET-positive CT-negative bone lesions. SM was confirmed in 36/41 (88%) PET-positive/CT-negative cases. This was based on biopsy, imaging, or clinical follow-up. The detection of PET-positive CT-negative SM did not change staging or management in 7/36 (19.4%). However, staging and/or management was affected in 29/36 (80.6%). CONCLUSION SM is not uncommon in 18F-FDG PET/CT, as it accounts for 146/2000 (7.3%) of cases. PET demonstrated FDG-avid SM without a CT abnormality in at least 36/146 (25%). Patients staging and/or management changed in 29/36 (80.5%). We concluded that 18F-FDG PET is sensitive in the detection of SM with significant impact on staging and/or management.
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Affiliation(s)
- Fatma Ahmed
- Saint Louis University , Saint Louis, MO , USA
| | | | | | - Yifan Tu
- Saint Louis University , Saint Louis, MO , USA
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