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magnetic resonance imaging in breast cancer: A review and meta-analysis
European Journal of Radiology 107 (2018) 158–165
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Staging/restaging performance of F18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in breast cancer: A review and meta-analysis Chun-Yi Lina,b, Cheng-Li Linc,d, Chia-Hung Kaoe,f,g,
T
⁎
a
School of Medicine, College of Medicine, Fu Jen Catholic University, Changhua, Taiwan Department of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan c Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan d College of Medicine, China Medical University, Taichung, Taiwan e Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan f Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan g Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan b
A R T I C LE I N FO
A B S T R A C T
Keywords: Breast cancer Fluorodeoxyglucose Positron emission tomography Magnetic resonance imaging
Purpose: This systematic review and meta-analysis was performed to assess the staging/restaging performance of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) in breast cancer. Methods: A comprehensive search was performed in PubMed databases for studies reporting the staging performance of F18-FDG PET/MRI in breast cancer from the inception of these databases to January 29, 2018. Eight studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of F18-FDG PET/MRI were calculated alongside 95% confidence intervals (CIs). A summary receiver operating characteristic curve (SROC) was plotted and the area under the SROC curve (AUC) was determined alongside the Q* index. Results: The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.98 (95% CI, 0.95–0.99), 0.87 (95% CI, 0.76–0.95), 4.59 (95% CI, 1.91–11.05), 0.03 (95% CI, 0.01–0.09), 203.07 (95% CI, 50.33–819.38), and 0.99, respectively. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.91 (95% CI, 0.88–0.94), 0.95 (95% CI, 0.92–0.97), 11.28 (95% CI, 4.25–29.96), 0.07 (95% CI, 0.02–0.22), 286.46 (95% CI, 64.15–1279.17), and 0.99, respectively. The overall diagnostic accuracies (Q* index) of the staging performance of F18-FDG PET/MRI in breast cancer were 0.96 (patient-based analysis) and 0.95 (lesion-based analysis). Conclusion: F18-FDG PET/MRI has excellent diagnostic staging/restaging performance in patients with breast cancer, and thus should be considered for staging of patients with breast cancer.
1. Introduction Breast cancer is the most common cancer type and leading cause of cancer-related deaths in women worldwide [1,2]. The incidence rate of
breast cancer is increasing rapidly [3]. Despite rising incidence, advanced screening and treatment modalities have contributed to the continuous decrease of breast cancer mortality in the Western world since the late 1980s [4,5]. Accurate staging is crucial because it affects
Abbreviations: AUC, area under curve; Cis, confidence intervals; CT, computed tomography; DOR, diagnostic odds ratio; FDG, fluorodeoxyglucose; NLR, negative likelihood ratio; MRI, magnetic resonance imaging; PET, positron emission tomography; PLR, positive likelihood ratio; SROC, summary receiver operating characteristic ⁎ Corresponding author at: Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. E-mail addresses: [email protected] (C.-Y. Lin), [email protected] (C.-L. Lin), [email protected], [email protected] (C.-H. Kao). https://doi.org/10.1016/j.ejrad.2018.09.003 Received 15 May 2018; Received in revised form 23 July 2018; Accepted 3 September 2018 0720-048X/ © 2018 Elsevier B.V. All rights reserved.
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2.3. Statistical analysis
not only the prognosis but also the type of surgery required, indications for systemic therapy, and the radiotherapy field. In the case of axillary lymph node metastasis in patients with breast cancer, the 5-year overall survival rate decreased from 98% to 85% from 2000 to 2015 [6]. Ultrasound, mammography, and magnetic resonance imaging (MRI) of breasts are routinely performed to evaluate the local tumor extent. Whole-body imaging through conventional imaging techniques, including bone scintigraphy, computed tomography (CT), and MRI, has traditionally been used to rule out distant metastases [1]. Furthermore, F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) provides functional data on tumor metabolism and has complementary value [7–9]. To overcome the limitations of morphological and functional imaging techniques, hybrid imaging systems have been developed and adopted into clinical routines [10,11]. Integrated F18-FDG PET/CT has been successfully introduced into the staging algorithms of a growing number of cancer types including breast cancer [12,13]. Despite the success of F18-FDG PET/CT, the possibility of replacing CT with MRI has been extensively investigated. MRI has several advantages over CT such as lower radiation exposure to patients, higher contrast resolution, and higher potential for function and molecular imaging [14–16]. In the preceding few years, MRI and PET of breasts have emerged as promising imaging tools [17–20]. More efficient imaging techniques for breast cancer could yield more accurate tumor staging, leading to further improvements in patient outcomes [7]. This study conducted a systematic review to examine the staging/restaging performance of F18-FDG PET/MRI in patients with breast cancer.
Statistical diagnostic parameters were estimated based on patients and lesions. Standard methods recommended for the meta-analysis of diagnostic test evaluations were performed. We used Meta-DiSc 1.4 (developed by the unit of Clinical Biostatistics team at Ramón y Cajal Hospital in Madrid, Spain) to perform statistical analyses [23,24]. Pooled measures for the following test indices were computed for each study: sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Furthermore, a summary receiver operating characteristic curve (SROC) was constructed and the area under the SROC curve (AUC) was determined. A perfect test had an AUC close to 1, whereas poor tests had an AUC close to 0.5 [1]. The random-effects model with a continuity correlation of 0.5 for zero frequencies was used for the statistical pooling of data [1]. Pooled data are presented with 95% confidence intervals (CIs). The AUC was calculated to measure the overall staging/restaging performance of F18-FDG PET/MRI in patients with breast cancer. The sensitivity and specificity of the single-test threshold identified for each study were used to plot the SROC curve along with the Q* index representing an overall measure of the test’s discriminatory power [25]. 3. Results 3.1. Literature search results The comprehensive literature search yielded 45 references in PubMed. Years of the 45 articles ranged from 2008 to 2018. After reviewing the titles and abstracts of these references, 13 articles were excluded for the following reasons: non-English articles (n = 2), unavailability of abstract (n = 2), review papers (n = 8), and case reports (n = 1). Thus, 32 articles were considered potentially relevant for this study. After reading the full texts of the 32 remaining studies, 24 were excluded for the following reasons: nonhuman studies (n = 8), non–F18-FDG PET/MRI diagnostic studies (n = 6), and insufficient diagnostic data (n = 10). The flowchart of the search and selection process is presented in Fig. 1. Of all 45 articles, only 8 were eligible based on the selection criteria. Table 1 lists the characteristics of the eight eligible studies. Five of these eight studies were prospective, whereas the other three had recruited patients retrospectively [26–32].
2. Materials and methods 2.1. Search strategy To identify all relevant publications, systematic searches in the bibliographic database PubMed were performed from its inception to January 29, 2018. Search terms included controlled terms from Mesh in PubMed, using “PET/MRI” in combination with “breast cancer.” All searches were limited to human studies. No informed consent or ethical committee approval was required because no patients were enrolled in this study.
2.2. Selection process 3.2. Quality assessment Two authors independently performed the searches and screening. Each published article was independently reviewed by two physicians to determine its eligibility for inclusion in the meta-analysis and to extract information regarding clinical patient data and F18-FDG PET/ MRI characteristics. From the selected studies, data on the first author, the year of publication, the number of patients included, patient age (mean/median), F18-FDG PET/MRI technical characteristics, and the number of lesions for evaluating the staging performance of F18-FDG PET/MRI in patients with breast cancer, including true negatives, false negatives, true positives, false positives, positive predictive value, and negative predictive value, were extracted and recorded. Any discrepancies were resolved through consensus. When there were discrepancies, they were resolved by consensus after joint reevaluation of the original studies by a third author [21]. F18-FDG PET/MRI studies that met the following criteria were included: studies that reported the staging/restaging performance of F18FDG PET/MRI in patients with breast cancer, clinical studies that included at least 10 patients [22], and studies that applied F18-FDG PET/ MRI as a dedicated device and were published after peer review. In vitro studies, animal studies, and studies without available full reports or reports written in non-English were excluded. Reviews, editorials, letters, legal cases, interviews, and case reports were not evaluated systematically in this review.
The results of the quality assessment performed using the QUADAS2 tool are listed in Table 2 [32]. The risk of patient selection was low in all included studies. The risk of bias with respect to the index test was low in all the studies because index test results were consistently interpreted without knowledge of the reference test outcome. The risk of bias for the reference test was low in seven of the included studies; one study was considered to have a high risk of bias because only follow-up imaging was used as the standard of reference. In general, only a few major concerns with respect to the risk of bias and applicability were noted. The quality of the currently available literature was considered reasonable. 3.3. Staging/restaging performance 3.3.1. Patient basis analysis The results of patient-based staging/restaging performance were reported in seven studies including a total of 283 patients with breast cancer. In the study conducted by Meisaether et al., two readers reported different diagnostic results. The more experienced reader detected more lesions, and thus the results reported by the more experienced reader were extracted into the pooled analysis in the present study. 159
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workup, local tumor extent, tumor spread, and nodal and distant metastases of primary or recurrent breast cancers should be determined to develop an appropriate and individualized therapeutic strategy for each patient [22]. Treatment choice is a complex procedure necessitating accurate staging and multidisciplinary team cooperation [27]. Imaging plays a crucial role in the staging and management of patients with breast cancer. Breast MRI is used to rule out additional malignancy sites in stage I cancers that might be occult at mammography. Other imaging techniques, including chest CT, bone scan, and abdominal CT or MRI, are recommended for stage I–IIB cancers in patients with pulmonary symptoms, bone pain, abnormal alkaline phosphatase levels, abnormal physical examinations, abnormal liver function, or abdominal symptoms. For stage IIIA, IV, and recurrent cancers, PET/CT is considered optional [31,35]. It has been reported that FDG PET/CT allowed combined metabolic and morphological assessment of breast cancer. FDG PET/CT improved diagnostic accuracy and had a significant impact on initial staging, management, retagging, early treatment response and prognosis in breast cancer patients [36]. Jo et al. reported that a high primary tumor SUVmax on FDG PET/CT was an independent factor correlated with worse disease-free survival in primary invasive ductal breast cancer patients. SUVmax 5.95 was the optimal cut-off value to predict disease-free survival on FDG PET/CT [37]. However, PET/CT requires a relatively high radiation dose and has low sensitivity for brain and liver lesions [30,38–42]. PET/MRI is a relatively recently developed hybrid imaging modality with significant clinical potential for the evaluation and management of cancer patients because of the potential for combining the excellent soft tissue contrast of MRI for local tumor staging with the accuracy of PET for distant staging [27]. PET/MRI enables improved diagnostic and staging accuracy in primary and metastatic cancers such as lymphomas and head and neck, bone, and liver tumors [43–49]. Furthermore, compared with PET/CT, PET/MRI may play a superior role in affecting oncologic management decisions [50,51]. Similar to other tumors, breast cancer has a high tumor glucose metabolism and glycolysis rate; these features render F18-FDG PET/MRI imaging suitable. The results of the present meta-analysis demonstrated a high diagnostic performance of F18-FDG PET/MRI for staging in patients with breast cancer. A high diagnostic performance clearly supports the role of F18-FDG PET/MRI in accurately staging not only primary tumors but also recurrent tumors in patients with breast cancer. It has been reported that for non-small cell lung cancer patients (NSCLC), the diagnostic accuracy of whole body PET/MRI ranged from 69% to 100% [52]. In the detection of liver lesions, Beiderwellen et al. reported that the accuracy of FDG PET/MRI was 96.1% [53]. Compared to the results of this study, the diagnostic performance of PET/MRI in NSCLC and liver lesions are similar to breast cancer patients. Giraudo et al. reported that FDG PET/MRI with diffusion weighted imaging (DWI) had an excellent sensitivity (100%) and diagnostic accuracy (100%) in lymphoma patients [54]. Brendle et al. reported that overall diagnostic accuracy was 69% in metastatic colorectal carcinoma on FDG PET/MRI [55]. According to the results of Brendle’s study, the diagnostic performance of FDG PET/MRI seems better in breast cancer than in colorectal carcinoma.
Fig. 1. Flowchart of the selection process of eligible studies.
The pooled sensitivity and specificity values were 0.98 (95% CI, 0.95–0.99; Fig. 2A) and 0.87 (95% CI, 0.76–0.95; Fig. 2B), respectively. The pooled PLR, NLR, and DOR were 4.59 (95% CI, 1.91–11.05), 0.03 (95% CI, 0.01–0.09), and 203.07 (95% CI, 50.33–819.38), respectively. The SROC curve representing the global summary score for test performance yielded an AUC of 0.99 and a Q* value of 0.96 (Fig. 2C), indicating a high level of overall accuracy. 3.3.2. Lesion basis analysis The results of lesion-based staging/restaging performance were reported in four studies including a total of 730 lesions. The pooled sensitivity and specificity values were 0.91 (95% CI, 0.88–0.94; Fig. 3A) and 0.95 (95% CI, 0.92–0.97; Fig. 3B), respectively. The PLR, NLR, and DOR were 11.28 (95% CI, 4.25–29.96), 0.07 (95% CI, 0.02–0.22), and 286.46 (95% CI, 64.15–1279.17), respectively. The SROC curve representing the global summary score for test performance yielded an AUC of 0.99 and a Q* value of 0.95 (Fig. 3C), respectively, indicating a high level of overall accuracy. 4. Discussion In Asian countries, breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths in women [33,34]. Patients’ prognoses and treatment strategies are based on the biology and stage of tumors. In addition to extensive histopathological Table 1 Characteristics of eligible studies. First author
Reference
Year
Study design
No. of patients
Mean/median age
Data type
Patients state
Grueneisen J Sawichi LM Pujara AC Botsikas D Melsaether AN Grueneisen L Goorts B Catalano OA
[25] [1] [26] [27] [28] [29] [30] [31]
2015 2015 2016 2016 2016 2017 2017 2017
Prospective Prospective Retrospective Retrospective Prospective Prospective Prospective Retrospective
49 21 35 58 51 36 40 51
56 years 59.4 years 58 years 47.4 years 56.27 years 58 years 50 years 53 years
Patient & lesion-based Patient & lesion-based Patient-based Lesion-based Patient-based Patient & lesion-based Patient-based Patient-based
Primary/new disease Recurrence/metastatic disease Metastatic disease Primary and metastatic diseases Metastatic disease Recurrence/metastatic disease New disease with metastases New disease with metastases
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Table 2 Quality assessment of included studies. First author
Year
Risk of bias
Applicability concerns
Patient selection
Index test
Reference standard
Flow and timing
Patient selection
Index test
Reference standard
Grueneisen J Sawichi LM Pujara AC Botsikas D Melsaether AN Grueneisen L Goorts B Catalano OA
2015 2015 2016 2016 2016 2017 2017 2017
Low Low Low Low Low Low Low Low
Low Low Low Low Low Low Low Low
Low Low High Low Low Low Low Low
Low Low Low Low Unclear Unclear Low Low
Low Low Low Low Low Low Low Low
Low Low Low Low Low Low Low Low
Low Low High Low Low Low Low Low
titled “Dedicated Breast PET/MRI in Evaluation of Extent of Disease in Women With Newly Diagnosed Breast Cancer” is to evaluate the specificity by adding breast FDG PET to MRI compared with breast MRI alone for the diagnosis on patients with newly diagnosed breast cancer [58]. Another one titled “PET-MRI for Axillary Staging in Node Negative Breast Cancer Patients” is to evaluate the accuracy of dedicated axillary hybrid PET/MRI to exclude axillary lymph node metastases in breast cancer patients [59].
In the current meta-analysis, the pooled sensitivities for staging of patients with breast cancer were 98% (patient-based analysis) and 91% (lesion-based analysis), indicating that a high proportion of positives were correctly identified through F18-FDG PET/MRI. A high pooled lesion-based specificity of 0.95 for staging through F18-FDG PET/MRI in patients with breast cancer was found in this study. The high diagnostic performance of F18-FDG PET/MRI in staging breast cancer is also justified by a high AUC of 0.99 in both patient- and lesion-based analyses. Based on the results of this study, F18-FDG PET/MRI should be considered for staging of patients with breast cancer. In previous studies, a clinically useful test was defined by a PLR higher than 5.0 and NLR lower than 0.2. The discrimination ability is higher with a higher PLR and lower NLR. In general, a PLR of more than 10 significantly increases the probability of a disease (“rule in” disease) for patients with positive results. A low NLR (less than 0.2) is clinically useful to rule out the possibility of a person having a disease [56,57]. The results of the present meta-analysis showed that lesion-based F18FDG PET/MRI had a high PLR (11.28), indicating that F18-FDG PET/ MRI findings suggesting malignant or metastatic lesions are likely to be confirmed through histopathological verification, clinical examination, or imaging follow-up. In the current study, both patient- and lesionbased analyses showed a low NLR (patient-based analysis, 0.03; lesionbased analysis, 0.07), indicating that negative F18-FDG PET/MRI results have outstanding value in ruling out suspicious lesions in patients with breast cancer. Compared with standard imaging modalities, axillary hybrid PET/MRI results in changes in nodal status as follows: 40% compared with ultrasound, 75% compared with T2-weighted MRI, 40% compared with contrast-enhanced MRI, and 22% compared with PET/ CT in patients with breast cancer [6]. According to the results of this meta-analysis, F18-FDG PET/MRI was valuable for downgrade staging in patients with breast cancer compared with conventional imaging modalities. This study had several limitations. First, positive result publication bias was a major concern because nonsignificant or unfavorable study results tend to be discarded. Thus the present study may overestimate the accuracy of the diagnosis. Second, there were only eight studies included in this study. The relatively small number of selected papers and various interpretation criteria may have caused variability in reported sensitivity and specificity values. The small number of evaluated studies and variability among them may have impaired the strength of the present meta-analysis. Third, not all included studies had a prospective study design. Further studies with prospective design are needed to update the review article. Fourth, biopsy results were not available for all lesions; some lesions were evaluated through clinical follow-up, which may have included various imaging modalities and clinical examinations. More studies with biopsy results are warranted to strengthen research power. Fifth, the generalizability of the results may have been affected by clinical heterogeneity. Upon more studies with clear recorded clinical characteristics are available, further analysis can be carried out according to specific clinical features. There are ongoing clinical trials to evaluate the diagnostic performance on FDG PET/MRI in breast cancer patients in the world. One
5. Conclusion Overall, F18-FDG PET/MRI demonstrated high diagnostic performance for accurate staging/restaging in patients with breast cancer. F18-FDG PET/MRI should be considered for staging of patients with breast cancer. To validate this high staging performance of F18-FDG PET/MRI in patients with breast cancer, larger prospective studies and additional assessments of patient subgroups with particular clinical benefits from applying this advanced imaging procedure are required. Funding This study was fundedby grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192); Academia Sinica Stroke Biosignature Project (BM10701010021); MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005-); Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan; China Medical University Hospital (CRS-106039, CRS-106-041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Conflict of interest Chun-Yi Lin declares that he/she has no conflict of interest. ChengLi Lin declares that he/she has no conflict of interest. Chia-Hung Kao declares that he/she has no conflict of interest. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Author contributions All authors have contributed substantially to, and are in agreement with the content of, the manuscript: Conception/Design: Chun-Yi Lin, Chia-Hung Kao; Provision of study materials: Chia-Hung Kao; Collection and/or assembly of data: All authors; Data analysis and interpretation: All authors; Manuscript preparation: All authors; Final approval of manuscript: All authors. The guarantor of the paper, taking responsibility for the integrity of the work as a whole, 161
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Fig. 2. Patient-based: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Individual study estimates of sensitivity and specificity of F18-FDG PET/MRI for staging performance in breast cancer.
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Fig. 3. Lesion-based: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Individual study estimates of sensitivity and specificity of F18-FDG PET/MRI for staging performance in breast cancer.
from inception to published article: Chia-Hung Kao.
2893–2917. [3] L.H. Chien, T.J. Tseng, C.H. Chen, H.F. Jiang, F.Y. Tsai, T.W. Liu, C.A. Hsiung, I.S. Chang, Comparison of annual percentage change in breast cancer incidence rate between Taiwan and the United States-A smoothed Lexis diagram approach, Cancer Med. 6 (2017) 1762–1775. [4] A. Katalinic, R. Pritzkuleit, A. Waldmann, Recent trends in breast Cancer incidence and mortality in Germany, Breast Care (Basel) 4 (2009) 75–80. [5] C.E. DeSantis, F. Bray, J. Ferlay, J. Lortet-Tieulent, B.O. Anderson, A. Jemal, International variation in female breast Cancer incidence and mortality rates, Cancer Epidemiol. Biomarkers Prev. 24 (2015) 1495–1506. [6] T.J.A. van Nijnatten, B. Goorts, S. Vöö, M. de Boer, L.F.S. Kooreman, E.M. Heuts,
References [1] L.M. Sawicki, J. Grueneisen, B.M. Schaarschmidt, C. Buchbender, J. Nagarajah, L. Umutlu, G. Antoch, S. Kinner, Evaluation of 18F-FDG PET/MRI, 18F-FDG PET/CT, MRI, and CT in whole-body staging of recurrent breast cancer, Eur. J. Radiol. 85 (2016) 459–465. [2] J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer 127 (2010)
163
European Journal of Radiology 107 (2018) 158–165
C.-Y. Lin et al.
[7]
[8]
[9] [10]
[11]
[12] [13] [14]
[15] [16] [17] [18]
[19]
[20]
[21]
[22]
[23]
[24] [25]
[26]
[27]
[28]
[29]
[30]
J.E. Wildberger, F.M. Mottaghy, M.B.I. Lobbes, M.L. Smidt, Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients: a feasibility study, Eur. J. Nucl. Med. Mol. Imaging 45 (2018) 179–186. K. Pinker, W. Bogner, P. Baltzer, G. Karanikas, H. Magometschnigg, P. Brader, S. Gruber, H. Bickel, P. Dubsky, Z. Bago-Horvath, R. Bartsch, M. Weber, S. Trattnig, T.H. Helbich, Improved differentiation of benign and malignant breast tumors with multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging: a feasibility study, Clin. Cancer Res. 20 (2014) 3540–3549. L. Moy, F. Ponzo, M.E. Noz, G.Q. Maguire Jr, A.D. Murphy-Walcott, A.E. Deans, M.T. Kitazono, L. Travascio, E.L. Kramer, Improving specificity of breast MRI using prone PET and fused MRI and PET 3D volume datasets, J. Nucl. Med. 48 (2007) 528–537. R. Kumar, N. Lal, A. Alavi, 18F-FDG PET in detecting primary breast cancer, J. Nucl. Med. 48 (2007) 1751; author reply 1752. H.F. Wehrl, M.S. Judenhofer, S. Wiehr, B.J. Pichler, Pre-clinical PET/MR: technological advances and new perspectives in biomedical research, Eur. J. Nucl. Med. Mol. Imaging 36 (Suppl 1) (2009) S56–68. M.S. Judenhofer, H.F. Wehrl, D.F. Newport, C. Catana, S.B. Siegel, M. Becker, A. Thielscher, M. Kneilling, M.P. Lichy, M. Eichner, K. Klingel, G. Reischl, S. Widmaier, M. Röcken, R.E. Nutt, H.J. Machulla, K. Uludag, S.R. Cherry, C.D. Claussen, B.J. Pichler, Simultaneous PET-MRI: a new approach for functional and morphological imaging, Nat. Med. 14 (2008) 459–465. C.D. Collins, PET/CT in oncology: for which tumours is it the reference standard? Cancer Imaging 7 (Spec No A) (2007) S77–87. G.K. von Schulthess, H.C. Steinert, T.F. Hany, Integrated PET/CT: current applications and future directions, Radiology 238 (2006) 405–422 Review. L. Pace, E. Nicolai, A. Luongo, M. Aiello, O.A. Catalano, A. Soricelli, M. Salvatore, Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues, Eur. J. Radiol. 83 (2014) 289–296. G.K. von Schulthess, H.P. Schlemmer, A look ahead: PET/MR versus PET/CT, Eur. J. Nucl. Med. Mol. Imaging 36 (Suppl 1) (2009) S3–S9. H. Herzog, PET/MRI: challenges, solutions and perspectives, Z. Med. Phys. 22 (2012) 281–298. E.A. Morris, Diagnostic breast MR imaging: current status and future directions, Radiol. Clin. North Am. 45 (2007) 863–880 vii. F. Sardanelli, C. Boetes, B. Borisch, T. Decker, M. Federico, F.J. Gilbert, T. Helbich, S.H. Heywang-Köbrunner, W.A. Kaiser, M.J. Kerin, R.E. Mansel, L. Marotti, L. Martincich, L. Mauriac, H. Meijers-Heijboer, R. Orecchia, P. Panizza, A. Ponti, A.D. Purushotham, P. Regitnig, M.R. Del Turco, F. Thibault, R. Wilson, Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group, Eur. J. Cancer 46 (2010) 1296–1316. N. Avril, L.P. Adler, F-18 fluorodeoxyglucose-positron emission tomography imaging for primary breast cancer and loco-regional staging, Radiol. Clin. North Am. 45 (2007) 645–657 vi. A.A. Zytoon, K. Murakami, M.R. El-Kholy, E. El-Shorbagy, Dual time point FDGPET/CT imaging… Potential tool for diagnosis of breast cancer, Clin. Radiol. 63 (2008) 1213–1227. B. Zhu, B. Zhu, C. Xiao, Z. Zheng, Vitamin D deficiency is associated with the severity of COPD: a systematic review and meta-analysis, Int. J. Chron. Obstruct. Pulmon. Dis. 10 (2015) 1907–1916. A.M. García Vicente, R.C. Delgado-Bolton, M. Amo-Salas, J. López-Fidalgo, A.P. Caresia Aróztegui, J.R. García Garzón, J. Orcajo Rincón, M.J. García Velloso, M. de Arcocha Torres, S. Alvárez Ruíz, Oncology Task Force of Spanish Society of Nuclear Medicine and Molecular Imaging, 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of malignancy in patients with paraneoplastic neurological syndrome: a systematic review and meta-analysis, Eur. J. Nucl. Med. Mol. Imaging 44 (2017) 1575–1587. W.L. Devillé, F. Buntinx, L.M. Bouter, V.M. Montori, H.C. de Vet, D.A. van der Windt, P.D. Bezemer, Conducting systematic reviews of diagnostic studies: didactic guidelines, BMC Med. Res. Methodol. 2 (2002) 9. J. Zamora, V. Abraira, A. Muriel, K. Khan, A. Coomarasamy, Meta-DiSc: a software for meta-analysis of test accuracy data, BMC Med. Res. Methodol. 6 (2006) 31. V.R. Bollineni, S. Ytre-Hauge, O. Bollineni-Balabay, H.B. Salvesen, I.S. Haldorsen, High diagnostic value of 18F-FDG PET/CT in endometrial Cancer: systematic review and meta-analysis of the literature, J. Nucl. Med. 57 (2016) 879–885. J. Grueneisen, J. Nagarajah, C. Buchbender, O. Hoffmann, B.M. Schaarschmidt, T. Poeppel, M. Forsting, H.H. Quick, L. Umutlu, S. Kinner, Positron Emission Tomography/Magnetic Resonance Imaging for Local Tumor Staging in Patients With Primary Breast Cancer: A Comparison With Positron Emission Tomography/ Computed Tomography and Magnetic Resonance Imaging, Invest. Radiol. 50 (2015) 505–513. A.C. Pujara, R.A. Raad, F. Ponzo, C. Wassong, J.S. Babb, L. Moy, A.N. Melsaether, Standardized uptake values from PET/MRI in metastatic breast Cancer: an organbased comparison with PET/CT, Breast J. 22 (2016) 264–273. D. Botsikas, A. Kalovidouri, M. Becker, M. Copercini, D.A. Djema, A. Bodmer, S. Monnier, C.D. Becker, X. Montet, B.M. Delattre, O. Ratib, V. Garibotto, C. Tabouret-Viaud, Clinical utility of 18F-FDG-PET/MR for preoperative breast cancer staging, Eur. Radiol. 26 (2016) 2297–2307. A.N. Melsaether, R.A. Raad, A.C. Pujara, F.D. Ponzo, K.M. Pysarenko, K. Jhaveri, J.S. Babb, E.E. Sigmund, S.G. Kim, L.A. Moy, Comparison of whole-body (18)F FDG PET/MR imaging and whole-body (18)F FDG PET/CT in terms of lesion detection and radiation dose in patients with breast Cancer, Radiology. 281 (2016) 193–202. B. Goorts, S. Vöö, T.J.A. van Nijnatten, L.F.S. Kooreman, M. de Boer, K.B.M.I. Keymeulen, R. Aarnoutse, J.E. Wildberger, F.M. Mottaghy, M.B.I. Lobbes,
[31]
[32]
[33]
[34] [35]
[36] [37]
[38] [39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
164
M.L. Smidt, Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy, Eur. J. Nucl. Med. Mol. Imaging 44 (2017) 1796–1805. O.A. Catalano, D. Daye, A. Signore, C. Iannace, M. Vangel, A. Luongo, M. Catalano, M. Filomena, L. Mansi, A. Soricelli, M. Salvatore, N. Fuin, C. Catana, U. Mahmood, B.R. Rosen, Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast, Int. J. Oncol. 51 (2017) 281–288. L. Goense, P.S. van Rossum, J.B. Reitsma, M.G. Lam, G.J. Meijer, M. van Vulpen, J.P. Ruurda, R. van Hillegersberg, Diagnostic performance of 18F-FDG PET and PET/CT for the detection of recurrent esophageal Cancer After treatment with curative intent: a systematic review and meta-analysis, J. Nucl. Med. 56 (2015) 995–1002. H.R. Shin, C. Joubert, M. Boniol, C. Hery, S.H. Ahn, Y.J. Won, Y. Nishino, T. Sobue, C.J. Chen, S.L. You, M.R. Mirasol-Lumague, S.C. Law, O. Mang, Y.B. Xiang, K.S. Chia, S. Rattanamongkolgul, J.G. Chen, M.P. Curado, P. Autier, Recent trends and patterns in breast cancer incidence among Eastern and Southeastern Asian women, Cancer Causes Control 21 (2010) 1777–1785. F. Bray, P. McCarron, D.M. Parkin, The changing global patterns of female breast cancer incidence and mortality, Breast Cancer Res. 6 (2004) 229–239. NCCN: Clinical Practice Guidelines in oncology 2016. https://www.nccn.org/ patients/guidelines/stage_i_ii_breast/files/assets/common/downloads/files/ stageibreast.pdf Accessed on Febuary. 26, 2018. K. Kitajima, Y. Miyoshi, Present and future role of FDG-PET/CT imaging in the management of breast cancer, J. Radiol. 34 (2016) 167–180. H.S. Kim, A.Y. Lee, J.E. Jo, B.C. Moon, Y. Ji, H.K. Kim, Optimization of ultrasonicassisted extraction of continentalic acid from the root of Aralia continentalis by using the response surface methodology, Arch. Pharm. Res. 37 (2014) 1437–1444. B. Huang, M.W. Law, P.L. Khong, Whole-body PET/CT scanning: estimation of radiation dose and cancer risk, Radiology 251 (2009) 166–174. G. Brix, U. Lechel, G. Glatting, S.I. Ziegler, W. Münzing, S.P. Müller, T. Beyer, Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations, J. Nucl. Med. 46 (2005) 608–613. L.K. Griffeth, K.M. Rich, F. Dehdashti, J.R. Simpson, M.J. Fusselman, A.H. McGuire, B.A. Siegel, Brain metastases from non-central nervous system tumors: evaluation with PET, Radiology. 186 (1993) 37–44. K. Kitajima, Y. Nakamoto, H. Okizuka, Y. Onishi, M. Senda, N. Suganuma, K. Sugimura, Accuracy of whole-body FDG-PET/CT for detecting brain metastases from non-central nervous system tumors, Ann. Nucl. Med. 22 (2008) 595–602. E.D. Rappeport, A. Loft, A.K. Berthelsen, P. von der Recke, P.N. Larsen, A.M. Mogensen, A. Wettergren, A. Rasmussen, J. Hillingsoe, P. Kirkegaard, C. Thomsen, Contrast-enhanced FDG-PET/CT vs. SPIO-enhanced MRI vs. FDG-PET vs. CT in patients with liver metastases from colorectal cancer: a prospective study with intraoperative confirmation, Acta Radiol. 48 (2007) 369–378. A. Boss, S. Bisdas, A. Kolb, M. Hofmann, U. Ernemann, C.D. Claussen, C. Pfannenberg, B.J. Pichler, M. Reimold, L. Stegger, Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT, J. Nucl. Med. 51 (2010) 1198–1205. A. Boss, L. Stegger, S. Bisdas, A. Kolb, N. Schwenzer, M. Pfister, C.D. Claussen, B.J. Pichler, C. Pfannenberg, Feasibility of simultaneous PET/MR imaging in the head and upper neck area, Eur. Radiol. 21 (2011) 1439–1446. L. Heacock, J. Weissbrot, R. Raad, N. Campbell, K.P. Friedman, F. Ponzo, H. Chandarana, PET/MRI for the evaluation of patients with lymphoma: initial observations, AJR Am. J. Roentgenol. 204 (2015) 842–848. A. Drzezga, M. Souvatzoglou, M. Eiber, A.J. Beer, S. Fürst, A. Martinez-Möller, S.G. Nekolla, S. Ziegler, C. Ganter, E.J. Rummeny, M. Schwaiger, First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses, J. Nucl. Med. 53 (2012) 845–855. C. Buchbender, T.A. Heusner, T.C. Lauenstein, A. Bockisch, G. Antoch, Oncologic PET/MRI, part 2: bone tumors, soft-tissue tumors, melanoma, and lymphoma, J. Nucl. Med. 53 (2012) 1244–1252. C. Buchbender, T.A. Heusner, T.C. Lauenstein, A. Bockisch, G. Antoch, Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen, and pelvis, J. Nucl. Med. 53 (2012) 928–938. M.W. Huellner, P. Appenzeller, F.P. Kuhn, L. Husmann, C.M. Pietsch, I.A. Burger, M. Porto, G. Delso, G.K. von Schulthess, P. Veit-Haibach, Whole-body nonenhanced PET/MR versus PET/CT in the staging and restaging of cancers: preliminary observations, Radiology 273 (2014) 859–869. O.A. Catalano, B.R. Rosen, D.V. Sahani, P.F. Hahn, A.R. Guimaraes, M.G. Vangel, E. Nicolai, A. Soricelli, M. Salvatore, Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients–a hypothesis-generating exploratory study, Radiology 269 (2013) 857–869. S.I. Lee, O.A. Catalano, F. Dehdashti, Evaluation of gynecologic cancer with MR imaging, 18F-FDG PET/CT, and PET/ MR imaging, J. Nucl. Med. 56 (2015) 436–443. Y. Ohno, H. Koyama, H.Y. Lee, T. Yoshikawa, K. Sugimura, Magnetic resonance imaging (MRI) and positron emission tomography (PET)/MRI for lung Cancer Staging, J. Thorac. Imaging 31 (2016) 215–227. K. Beiderwellen, L. Geraldo, V. Ruhlmann, P. Heusch, B. Gomez, F. Nensa, L. Umutlu, T.C. Lauenstein, Accuracy of [18F]FDG PET/MRI for the detection of liver metastases, PLoS ONE 10 (2015) e0137285. C. Giraudo, M. Raderer, G. Karanikas, M. Weber, B. Kiesewetter, W. Dolak, I. Simonitsch-Klupp, M.E. Mayerhoefer, 18F-fluorodeoxyglucose positron emission Tomography/Magnetic resonance in lymphoma: comparison with 18FFluorodeoxyglucose positron emission Tomography/Computed tomography and with the addition of magnetic resonance diffusion-weighted imaging, Invest. Radiol. 51 (2016) 163–169.
European Journal of Radiology 107 (2018) 158–165
C.-Y. Lin et al.
with cervical carcinoma: a metaanalysis, J. Nucl. Med. 51 (2010) 360–367. [57] A.K. Akobeng, Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice, Acta Paediatr. 96 (2007) 487–491. [58] https://clinicaltrials.gov/ct2/show/NCT03510988 Accessed on July, 19th 2018. [59] https://clinicaltrials.gov/ct2/show/NCT03374826?term=PET%2FMRI&cond= Breast+Cancer&rank=4 Accessed on July, 19th 2018.
[55] C. Brendle, N.F. Schwenzer, H. Rempp, H. Schmidt, C. Pfannenberg, C. la Fougère, K. Nikolaou, C. Schraml, Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series, Eur. J. Nucl. Med. Mol. Imaging 43 (2016) 123–132. [56] S. Kang, S.K. Kim, D.C. Chung, S.S. Seo, J.Y. Kim, B.H. Nam, S.Y. Park, Diagnostic value of (18)F-FDG PET for evaluation of paraaortic nodal metastasis in patients
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Staging/restaging performance of F18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in breast cancer: A review and meta-analysis Chun-Yi Lina,b, Cheng-Li Linc,d, Chia-Hung Kaoe,f,g,
T
⁎
a
School of Medicine, College of Medicine, Fu Jen Catholic University, Changhua, Taiwan Department of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan c Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan d College of Medicine, China Medical University, Taichung, Taiwan e Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan f Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan g Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan b
A R T I C LE I N FO
A B S T R A C T
Keywords: Breast cancer Fluorodeoxyglucose Positron emission tomography Magnetic resonance imaging
Purpose: This systematic review and meta-analysis was performed to assess the staging/restaging performance of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) in breast cancer. Methods: A comprehensive search was performed in PubMed databases for studies reporting the staging performance of F18-FDG PET/MRI in breast cancer from the inception of these databases to January 29, 2018. Eight studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of F18-FDG PET/MRI were calculated alongside 95% confidence intervals (CIs). A summary receiver operating characteristic curve (SROC) was plotted and the area under the SROC curve (AUC) was determined alongside the Q* index. Results: The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.98 (95% CI, 0.95–0.99), 0.87 (95% CI, 0.76–0.95), 4.59 (95% CI, 1.91–11.05), 0.03 (95% CI, 0.01–0.09), 203.07 (95% CI, 50.33–819.38), and 0.99, respectively. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.91 (95% CI, 0.88–0.94), 0.95 (95% CI, 0.92–0.97), 11.28 (95% CI, 4.25–29.96), 0.07 (95% CI, 0.02–0.22), 286.46 (95% CI, 64.15–1279.17), and 0.99, respectively. The overall diagnostic accuracies (Q* index) of the staging performance of F18-FDG PET/MRI in breast cancer were 0.96 (patient-based analysis) and 0.95 (lesion-based analysis). Conclusion: F18-FDG PET/MRI has excellent diagnostic staging/restaging performance in patients with breast cancer, and thus should be considered for staging of patients with breast cancer.
1. Introduction Breast cancer is the most common cancer type and leading cause of cancer-related deaths in women worldwide [1,2]. The incidence rate of
breast cancer is increasing rapidly [3]. Despite rising incidence, advanced screening and treatment modalities have contributed to the continuous decrease of breast cancer mortality in the Western world since the late 1980s [4,5]. Accurate staging is crucial because it affects
Abbreviations: AUC, area under curve; Cis, confidence intervals; CT, computed tomography; DOR, diagnostic odds ratio; FDG, fluorodeoxyglucose; NLR, negative likelihood ratio; MRI, magnetic resonance imaging; PET, positron emission tomography; PLR, positive likelihood ratio; SROC, summary receiver operating characteristic ⁎ Corresponding author at: Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. E-mail addresses: [email protected] (C.-Y. Lin), [email protected] (C.-L. Lin), [email protected], [email protected] (C.-H. Kao). https://doi.org/10.1016/j.ejrad.2018.09.003 Received 15 May 2018; Received in revised form 23 July 2018; Accepted 3 September 2018 0720-048X/ © 2018 Elsevier B.V. All rights reserved.
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2.3. Statistical analysis
not only the prognosis but also the type of surgery required, indications for systemic therapy, and the radiotherapy field. In the case of axillary lymph node metastasis in patients with breast cancer, the 5-year overall survival rate decreased from 98% to 85% from 2000 to 2015 [6]. Ultrasound, mammography, and magnetic resonance imaging (MRI) of breasts are routinely performed to evaluate the local tumor extent. Whole-body imaging through conventional imaging techniques, including bone scintigraphy, computed tomography (CT), and MRI, has traditionally been used to rule out distant metastases [1]. Furthermore, F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) provides functional data on tumor metabolism and has complementary value [7–9]. To overcome the limitations of morphological and functional imaging techniques, hybrid imaging systems have been developed and adopted into clinical routines [10,11]. Integrated F18-FDG PET/CT has been successfully introduced into the staging algorithms of a growing number of cancer types including breast cancer [12,13]. Despite the success of F18-FDG PET/CT, the possibility of replacing CT with MRI has been extensively investigated. MRI has several advantages over CT such as lower radiation exposure to patients, higher contrast resolution, and higher potential for function and molecular imaging [14–16]. In the preceding few years, MRI and PET of breasts have emerged as promising imaging tools [17–20]. More efficient imaging techniques for breast cancer could yield more accurate tumor staging, leading to further improvements in patient outcomes [7]. This study conducted a systematic review to examine the staging/restaging performance of F18-FDG PET/MRI in patients with breast cancer.
Statistical diagnostic parameters were estimated based on patients and lesions. Standard methods recommended for the meta-analysis of diagnostic test evaluations were performed. We used Meta-DiSc 1.4 (developed by the unit of Clinical Biostatistics team at Ramón y Cajal Hospital in Madrid, Spain) to perform statistical analyses [23,24]. Pooled measures for the following test indices were computed for each study: sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Furthermore, a summary receiver operating characteristic curve (SROC) was constructed and the area under the SROC curve (AUC) was determined. A perfect test had an AUC close to 1, whereas poor tests had an AUC close to 0.5 [1]. The random-effects model with a continuity correlation of 0.5 for zero frequencies was used for the statistical pooling of data [1]. Pooled data are presented with 95% confidence intervals (CIs). The AUC was calculated to measure the overall staging/restaging performance of F18-FDG PET/MRI in patients with breast cancer. The sensitivity and specificity of the single-test threshold identified for each study were used to plot the SROC curve along with the Q* index representing an overall measure of the test’s discriminatory power [25]. 3. Results 3.1. Literature search results The comprehensive literature search yielded 45 references in PubMed. Years of the 45 articles ranged from 2008 to 2018. After reviewing the titles and abstracts of these references, 13 articles were excluded for the following reasons: non-English articles (n = 2), unavailability of abstract (n = 2), review papers (n = 8), and case reports (n = 1). Thus, 32 articles were considered potentially relevant for this study. After reading the full texts of the 32 remaining studies, 24 were excluded for the following reasons: nonhuman studies (n = 8), non–F18-FDG PET/MRI diagnostic studies (n = 6), and insufficient diagnostic data (n = 10). The flowchart of the search and selection process is presented in Fig. 1. Of all 45 articles, only 8 were eligible based on the selection criteria. Table 1 lists the characteristics of the eight eligible studies. Five of these eight studies were prospective, whereas the other three had recruited patients retrospectively [26–32].
2. Materials and methods 2.1. Search strategy To identify all relevant publications, systematic searches in the bibliographic database PubMed were performed from its inception to January 29, 2018. Search terms included controlled terms from Mesh in PubMed, using “PET/MRI” in combination with “breast cancer.” All searches were limited to human studies. No informed consent or ethical committee approval was required because no patients were enrolled in this study.
2.2. Selection process 3.2. Quality assessment Two authors independently performed the searches and screening. Each published article was independently reviewed by two physicians to determine its eligibility for inclusion in the meta-analysis and to extract information regarding clinical patient data and F18-FDG PET/ MRI characteristics. From the selected studies, data on the first author, the year of publication, the number of patients included, patient age (mean/median), F18-FDG PET/MRI technical characteristics, and the number of lesions for evaluating the staging performance of F18-FDG PET/MRI in patients with breast cancer, including true negatives, false negatives, true positives, false positives, positive predictive value, and negative predictive value, were extracted and recorded. Any discrepancies were resolved through consensus. When there were discrepancies, they were resolved by consensus after joint reevaluation of the original studies by a third author [21]. F18-FDG PET/MRI studies that met the following criteria were included: studies that reported the staging/restaging performance of F18FDG PET/MRI in patients with breast cancer, clinical studies that included at least 10 patients [22], and studies that applied F18-FDG PET/ MRI as a dedicated device and were published after peer review. In vitro studies, animal studies, and studies without available full reports or reports written in non-English were excluded. Reviews, editorials, letters, legal cases, interviews, and case reports were not evaluated systematically in this review.
The results of the quality assessment performed using the QUADAS2 tool are listed in Table 2 [32]. The risk of patient selection was low in all included studies. The risk of bias with respect to the index test was low in all the studies because index test results were consistently interpreted without knowledge of the reference test outcome. The risk of bias for the reference test was low in seven of the included studies; one study was considered to have a high risk of bias because only follow-up imaging was used as the standard of reference. In general, only a few major concerns with respect to the risk of bias and applicability were noted. The quality of the currently available literature was considered reasonable. 3.3. Staging/restaging performance 3.3.1. Patient basis analysis The results of patient-based staging/restaging performance were reported in seven studies including a total of 283 patients with breast cancer. In the study conducted by Meisaether et al., two readers reported different diagnostic results. The more experienced reader detected more lesions, and thus the results reported by the more experienced reader were extracted into the pooled analysis in the present study. 159
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workup, local tumor extent, tumor spread, and nodal and distant metastases of primary or recurrent breast cancers should be determined to develop an appropriate and individualized therapeutic strategy for each patient [22]. Treatment choice is a complex procedure necessitating accurate staging and multidisciplinary team cooperation [27]. Imaging plays a crucial role in the staging and management of patients with breast cancer. Breast MRI is used to rule out additional malignancy sites in stage I cancers that might be occult at mammography. Other imaging techniques, including chest CT, bone scan, and abdominal CT or MRI, are recommended for stage I–IIB cancers in patients with pulmonary symptoms, bone pain, abnormal alkaline phosphatase levels, abnormal physical examinations, abnormal liver function, or abdominal symptoms. For stage IIIA, IV, and recurrent cancers, PET/CT is considered optional [31,35]. It has been reported that FDG PET/CT allowed combined metabolic and morphological assessment of breast cancer. FDG PET/CT improved diagnostic accuracy and had a significant impact on initial staging, management, retagging, early treatment response and prognosis in breast cancer patients [36]. Jo et al. reported that a high primary tumor SUVmax on FDG PET/CT was an independent factor correlated with worse disease-free survival in primary invasive ductal breast cancer patients. SUVmax 5.95 was the optimal cut-off value to predict disease-free survival on FDG PET/CT [37]. However, PET/CT requires a relatively high radiation dose and has low sensitivity for brain and liver lesions [30,38–42]. PET/MRI is a relatively recently developed hybrid imaging modality with significant clinical potential for the evaluation and management of cancer patients because of the potential for combining the excellent soft tissue contrast of MRI for local tumor staging with the accuracy of PET for distant staging [27]. PET/MRI enables improved diagnostic and staging accuracy in primary and metastatic cancers such as lymphomas and head and neck, bone, and liver tumors [43–49]. Furthermore, compared with PET/CT, PET/MRI may play a superior role in affecting oncologic management decisions [50,51]. Similar to other tumors, breast cancer has a high tumor glucose metabolism and glycolysis rate; these features render F18-FDG PET/MRI imaging suitable. The results of the present meta-analysis demonstrated a high diagnostic performance of F18-FDG PET/MRI for staging in patients with breast cancer. A high diagnostic performance clearly supports the role of F18-FDG PET/MRI in accurately staging not only primary tumors but also recurrent tumors in patients with breast cancer. It has been reported that for non-small cell lung cancer patients (NSCLC), the diagnostic accuracy of whole body PET/MRI ranged from 69% to 100% [52]. In the detection of liver lesions, Beiderwellen et al. reported that the accuracy of FDG PET/MRI was 96.1% [53]. Compared to the results of this study, the diagnostic performance of PET/MRI in NSCLC and liver lesions are similar to breast cancer patients. Giraudo et al. reported that FDG PET/MRI with diffusion weighted imaging (DWI) had an excellent sensitivity (100%) and diagnostic accuracy (100%) in lymphoma patients [54]. Brendle et al. reported that overall diagnostic accuracy was 69% in metastatic colorectal carcinoma on FDG PET/MRI [55]. According to the results of Brendle’s study, the diagnostic performance of FDG PET/MRI seems better in breast cancer than in colorectal carcinoma.
Fig. 1. Flowchart of the selection process of eligible studies.
The pooled sensitivity and specificity values were 0.98 (95% CI, 0.95–0.99; Fig. 2A) and 0.87 (95% CI, 0.76–0.95; Fig. 2B), respectively. The pooled PLR, NLR, and DOR were 4.59 (95% CI, 1.91–11.05), 0.03 (95% CI, 0.01–0.09), and 203.07 (95% CI, 50.33–819.38), respectively. The SROC curve representing the global summary score for test performance yielded an AUC of 0.99 and a Q* value of 0.96 (Fig. 2C), indicating a high level of overall accuracy. 3.3.2. Lesion basis analysis The results of lesion-based staging/restaging performance were reported in four studies including a total of 730 lesions. The pooled sensitivity and specificity values were 0.91 (95% CI, 0.88–0.94; Fig. 3A) and 0.95 (95% CI, 0.92–0.97; Fig. 3B), respectively. The PLR, NLR, and DOR were 11.28 (95% CI, 4.25–29.96), 0.07 (95% CI, 0.02–0.22), and 286.46 (95% CI, 64.15–1279.17), respectively. The SROC curve representing the global summary score for test performance yielded an AUC of 0.99 and a Q* value of 0.95 (Fig. 3C), respectively, indicating a high level of overall accuracy. 4. Discussion In Asian countries, breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths in women [33,34]. Patients’ prognoses and treatment strategies are based on the biology and stage of tumors. In addition to extensive histopathological Table 1 Characteristics of eligible studies. First author
Reference
Year
Study design
No. of patients
Mean/median age
Data type
Patients state
Grueneisen J Sawichi LM Pujara AC Botsikas D Melsaether AN Grueneisen L Goorts B Catalano OA
[25] [1] [26] [27] [28] [29] [30] [31]
2015 2015 2016 2016 2016 2017 2017 2017
Prospective Prospective Retrospective Retrospective Prospective Prospective Prospective Retrospective
49 21 35 58 51 36 40 51
56 years 59.4 years 58 years 47.4 years 56.27 years 58 years 50 years 53 years
Patient & lesion-based Patient & lesion-based Patient-based Lesion-based Patient-based Patient & lesion-based Patient-based Patient-based
Primary/new disease Recurrence/metastatic disease Metastatic disease Primary and metastatic diseases Metastatic disease Recurrence/metastatic disease New disease with metastases New disease with metastases
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Table 2 Quality assessment of included studies. First author
Year
Risk of bias
Applicability concerns
Patient selection
Index test
Reference standard
Flow and timing
Patient selection
Index test
Reference standard
Grueneisen J Sawichi LM Pujara AC Botsikas D Melsaether AN Grueneisen L Goorts B Catalano OA
2015 2015 2016 2016 2016 2017 2017 2017
Low Low Low Low Low Low Low Low
Low Low Low Low Low Low Low Low
Low Low High Low Low Low Low Low
Low Low Low Low Unclear Unclear Low Low
Low Low Low Low Low Low Low Low
Low Low Low Low Low Low Low Low
Low Low High Low Low Low Low Low
titled “Dedicated Breast PET/MRI in Evaluation of Extent of Disease in Women With Newly Diagnosed Breast Cancer” is to evaluate the specificity by adding breast FDG PET to MRI compared with breast MRI alone for the diagnosis on patients with newly diagnosed breast cancer [58]. Another one titled “PET-MRI for Axillary Staging in Node Negative Breast Cancer Patients” is to evaluate the accuracy of dedicated axillary hybrid PET/MRI to exclude axillary lymph node metastases in breast cancer patients [59].
In the current meta-analysis, the pooled sensitivities for staging of patients with breast cancer were 98% (patient-based analysis) and 91% (lesion-based analysis), indicating that a high proportion of positives were correctly identified through F18-FDG PET/MRI. A high pooled lesion-based specificity of 0.95 for staging through F18-FDG PET/MRI in patients with breast cancer was found in this study. The high diagnostic performance of F18-FDG PET/MRI in staging breast cancer is also justified by a high AUC of 0.99 in both patient- and lesion-based analyses. Based on the results of this study, F18-FDG PET/MRI should be considered for staging of patients with breast cancer. In previous studies, a clinically useful test was defined by a PLR higher than 5.0 and NLR lower than 0.2. The discrimination ability is higher with a higher PLR and lower NLR. In general, a PLR of more than 10 significantly increases the probability of a disease (“rule in” disease) for patients with positive results. A low NLR (less than 0.2) is clinically useful to rule out the possibility of a person having a disease [56,57]. The results of the present meta-analysis showed that lesion-based F18FDG PET/MRI had a high PLR (11.28), indicating that F18-FDG PET/ MRI findings suggesting malignant or metastatic lesions are likely to be confirmed through histopathological verification, clinical examination, or imaging follow-up. In the current study, both patient- and lesionbased analyses showed a low NLR (patient-based analysis, 0.03; lesionbased analysis, 0.07), indicating that negative F18-FDG PET/MRI results have outstanding value in ruling out suspicious lesions in patients with breast cancer. Compared with standard imaging modalities, axillary hybrid PET/MRI results in changes in nodal status as follows: 40% compared with ultrasound, 75% compared with T2-weighted MRI, 40% compared with contrast-enhanced MRI, and 22% compared with PET/ CT in patients with breast cancer [6]. According to the results of this meta-analysis, F18-FDG PET/MRI was valuable for downgrade staging in patients with breast cancer compared with conventional imaging modalities. This study had several limitations. First, positive result publication bias was a major concern because nonsignificant or unfavorable study results tend to be discarded. Thus the present study may overestimate the accuracy of the diagnosis. Second, there were only eight studies included in this study. The relatively small number of selected papers and various interpretation criteria may have caused variability in reported sensitivity and specificity values. The small number of evaluated studies and variability among them may have impaired the strength of the present meta-analysis. Third, not all included studies had a prospective study design. Further studies with prospective design are needed to update the review article. Fourth, biopsy results were not available for all lesions; some lesions were evaluated through clinical follow-up, which may have included various imaging modalities and clinical examinations. More studies with biopsy results are warranted to strengthen research power. Fifth, the generalizability of the results may have been affected by clinical heterogeneity. Upon more studies with clear recorded clinical characteristics are available, further analysis can be carried out according to specific clinical features. There are ongoing clinical trials to evaluate the diagnostic performance on FDG PET/MRI in breast cancer patients in the world. One
5. Conclusion Overall, F18-FDG PET/MRI demonstrated high diagnostic performance for accurate staging/restaging in patients with breast cancer. F18-FDG PET/MRI should be considered for staging of patients with breast cancer. To validate this high staging performance of F18-FDG PET/MRI in patients with breast cancer, larger prospective studies and additional assessments of patient subgroups with particular clinical benefits from applying this advanced imaging procedure are required. Funding This study was fundedby grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192); Academia Sinica Stroke Biosignature Project (BM10701010021); MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005-); Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan; China Medical University Hospital (CRS-106039, CRS-106-041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Conflict of interest Chun-Yi Lin declares that he/she has no conflict of interest. ChengLi Lin declares that he/she has no conflict of interest. Chia-Hung Kao declares that he/she has no conflict of interest. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Author contributions All authors have contributed substantially to, and are in agreement with the content of, the manuscript: Conception/Design: Chun-Yi Lin, Chia-Hung Kao; Provision of study materials: Chia-Hung Kao; Collection and/or assembly of data: All authors; Data analysis and interpretation: All authors; Manuscript preparation: All authors; Final approval of manuscript: All authors. The guarantor of the paper, taking responsibility for the integrity of the work as a whole, 161
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Fig. 2. Patient-based: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Individual study estimates of sensitivity and specificity of F18-FDG PET/MRI for staging performance in breast cancer.
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Fig. 3. Lesion-based: forest plot of sensitivity pooling (A); forest plot of specificity pooling (B); SROC curve (C). Individual study estimates of sensitivity and specificity of F18-FDG PET/MRI for staging performance in breast cancer.
from inception to published article: Chia-Hung Kao.
2893–2917. [3] L.H. Chien, T.J. Tseng, C.H. Chen, H.F. Jiang, F.Y. Tsai, T.W. Liu, C.A. Hsiung, I.S. Chang, Comparison of annual percentage change in breast cancer incidence rate between Taiwan and the United States-A smoothed Lexis diagram approach, Cancer Med. 6 (2017) 1762–1775. [4] A. Katalinic, R. Pritzkuleit, A. Waldmann, Recent trends in breast Cancer incidence and mortality in Germany, Breast Care (Basel) 4 (2009) 75–80. [5] C.E. DeSantis, F. Bray, J. Ferlay, J. Lortet-Tieulent, B.O. Anderson, A. Jemal, International variation in female breast Cancer incidence and mortality rates, Cancer Epidemiol. Biomarkers Prev. 24 (2015) 1495–1506. [6] T.J.A. van Nijnatten, B. Goorts, S. Vöö, M. de Boer, L.F.S. Kooreman, E.M. Heuts,
References [1] L.M. Sawicki, J. Grueneisen, B.M. Schaarschmidt, C. Buchbender, J. Nagarajah, L. Umutlu, G. Antoch, S. Kinner, Evaluation of 18F-FDG PET/MRI, 18F-FDG PET/CT, MRI, and CT in whole-body staging of recurrent breast cancer, Eur. J. Radiol. 85 (2016) 459–465. [2] J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer 127 (2010)
163
European Journal of Radiology 107 (2018) 158–165
C.-Y. Lin et al.
[7]
[8]
[9] [10]
[11]
[12] [13] [14]
[15] [16] [17] [18]
[19]
[20]
[21]
[22]
[23]
[24] [25]
[26]
[27]
[28]
[29]
[30]
J.E. Wildberger, F.M. Mottaghy, M.B.I. Lobbes, M.L. Smidt, Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients: a feasibility study, Eur. J. Nucl. Med. Mol. Imaging 45 (2018) 179–186. K. Pinker, W. Bogner, P. Baltzer, G. Karanikas, H. Magometschnigg, P. Brader, S. Gruber, H. Bickel, P. Dubsky, Z. Bago-Horvath, R. Bartsch, M. Weber, S. Trattnig, T.H. Helbich, Improved differentiation of benign and malignant breast tumors with multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging: a feasibility study, Clin. Cancer Res. 20 (2014) 3540–3549. L. Moy, F. Ponzo, M.E. Noz, G.Q. Maguire Jr, A.D. Murphy-Walcott, A.E. Deans, M.T. Kitazono, L. Travascio, E.L. Kramer, Improving specificity of breast MRI using prone PET and fused MRI and PET 3D volume datasets, J. Nucl. Med. 48 (2007) 528–537. R. Kumar, N. Lal, A. Alavi, 18F-FDG PET in detecting primary breast cancer, J. Nucl. Med. 48 (2007) 1751; author reply 1752. H.F. Wehrl, M.S. Judenhofer, S. Wiehr, B.J. Pichler, Pre-clinical PET/MR: technological advances and new perspectives in biomedical research, Eur. J. Nucl. Med. Mol. Imaging 36 (Suppl 1) (2009) S56–68. M.S. Judenhofer, H.F. Wehrl, D.F. Newport, C. Catana, S.B. Siegel, M. Becker, A. Thielscher, M. Kneilling, M.P. Lichy, M. Eichner, K. Klingel, G. Reischl, S. Widmaier, M. Röcken, R.E. Nutt, H.J. Machulla, K. Uludag, S.R. Cherry, C.D. Claussen, B.J. Pichler, Simultaneous PET-MRI: a new approach for functional and morphological imaging, Nat. Med. 14 (2008) 459–465. C.D. Collins, PET/CT in oncology: for which tumours is it the reference standard? Cancer Imaging 7 (Spec No A) (2007) S77–87. G.K. von Schulthess, H.C. Steinert, T.F. Hany, Integrated PET/CT: current applications and future directions, Radiology 238 (2006) 405–422 Review. L. Pace, E. Nicolai, A. Luongo, M. Aiello, O.A. Catalano, A. Soricelli, M. Salvatore, Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues, Eur. J. Radiol. 83 (2014) 289–296. G.K. von Schulthess, H.P. Schlemmer, A look ahead: PET/MR versus PET/CT, Eur. J. Nucl. Med. Mol. Imaging 36 (Suppl 1) (2009) S3–S9. H. Herzog, PET/MRI: challenges, solutions and perspectives, Z. Med. Phys. 22 (2012) 281–298. E.A. Morris, Diagnostic breast MR imaging: current status and future directions, Radiol. Clin. North Am. 45 (2007) 863–880 vii. F. Sardanelli, C. Boetes, B. Borisch, T. Decker, M. Federico, F.J. Gilbert, T. Helbich, S.H. Heywang-Köbrunner, W.A. Kaiser, M.J. Kerin, R.E. Mansel, L. Marotti, L. Martincich, L. Mauriac, H. Meijers-Heijboer, R. Orecchia, P. Panizza, A. Ponti, A.D. Purushotham, P. Regitnig, M.R. Del Turco, F. Thibault, R. Wilson, Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group, Eur. J. Cancer 46 (2010) 1296–1316. N. Avril, L.P. Adler, F-18 fluorodeoxyglucose-positron emission tomography imaging for primary breast cancer and loco-regional staging, Radiol. Clin. North Am. 45 (2007) 645–657 vi. A.A. Zytoon, K. Murakami, M.R. El-Kholy, E. El-Shorbagy, Dual time point FDGPET/CT imaging… Potential tool for diagnosis of breast cancer, Clin. Radiol. 63 (2008) 1213–1227. B. Zhu, B. Zhu, C. Xiao, Z. Zheng, Vitamin D deficiency is associated with the severity of COPD: a systematic review and meta-analysis, Int. J. Chron. Obstruct. Pulmon. Dis. 10 (2015) 1907–1916. A.M. García Vicente, R.C. Delgado-Bolton, M. Amo-Salas, J. López-Fidalgo, A.P. Caresia Aróztegui, J.R. García Garzón, J. Orcajo Rincón, M.J. García Velloso, M. de Arcocha Torres, S. Alvárez Ruíz, Oncology Task Force of Spanish Society of Nuclear Medicine and Molecular Imaging, 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of malignancy in patients with paraneoplastic neurological syndrome: a systematic review and meta-analysis, Eur. J. Nucl. Med. Mol. Imaging 44 (2017) 1575–1587. W.L. Devillé, F. Buntinx, L.M. Bouter, V.M. Montori, H.C. de Vet, D.A. van der Windt, P.D. Bezemer, Conducting systematic reviews of diagnostic studies: didactic guidelines, BMC Med. Res. Methodol. 2 (2002) 9. J. Zamora, V. Abraira, A. Muriel, K. Khan, A. Coomarasamy, Meta-DiSc: a software for meta-analysis of test accuracy data, BMC Med. Res. Methodol. 6 (2006) 31. V.R. Bollineni, S. Ytre-Hauge, O. Bollineni-Balabay, H.B. Salvesen, I.S. Haldorsen, High diagnostic value of 18F-FDG PET/CT in endometrial Cancer: systematic review and meta-analysis of the literature, J. Nucl. Med. 57 (2016) 879–885. J. Grueneisen, J. Nagarajah, C. Buchbender, O. Hoffmann, B.M. Schaarschmidt, T. Poeppel, M. Forsting, H.H. Quick, L. Umutlu, S. Kinner, Positron Emission Tomography/Magnetic Resonance Imaging for Local Tumor Staging in Patients With Primary Breast Cancer: A Comparison With Positron Emission Tomography/ Computed Tomography and Magnetic Resonance Imaging, Invest. Radiol. 50 (2015) 505–513. A.C. Pujara, R.A. Raad, F. Ponzo, C. Wassong, J.S. Babb, L. Moy, A.N. Melsaether, Standardized uptake values from PET/MRI in metastatic breast Cancer: an organbased comparison with PET/CT, Breast J. 22 (2016) 264–273. D. Botsikas, A. Kalovidouri, M. Becker, M. Copercini, D.A. Djema, A. Bodmer, S. Monnier, C.D. Becker, X. Montet, B.M. Delattre, O. Ratib, V. Garibotto, C. Tabouret-Viaud, Clinical utility of 18F-FDG-PET/MR for preoperative breast cancer staging, Eur. Radiol. 26 (2016) 2297–2307. A.N. Melsaether, R.A. Raad, A.C. Pujara, F.D. Ponzo, K.M. Pysarenko, K. Jhaveri, J.S. Babb, E.E. Sigmund, S.G. Kim, L.A. Moy, Comparison of whole-body (18)F FDG PET/MR imaging and whole-body (18)F FDG PET/CT in terms of lesion detection and radiation dose in patients with breast Cancer, Radiology. 281 (2016) 193–202. B. Goorts, S. Vöö, T.J.A. van Nijnatten, L.F.S. Kooreman, M. de Boer, K.B.M.I. Keymeulen, R. Aarnoutse, J.E. Wildberger, F.M. Mottaghy, M.B.I. Lobbes,
[31]
[32]
[33]
[34] [35]
[36] [37]
[38] [39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
164
M.L. Smidt, Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy, Eur. J. Nucl. Med. Mol. Imaging 44 (2017) 1796–1805. O.A. Catalano, D. Daye, A. Signore, C. Iannace, M. Vangel, A. Luongo, M. Catalano, M. Filomena, L. Mansi, A. Soricelli, M. Salvatore, N. Fuin, C. Catana, U. Mahmood, B.R. Rosen, Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast, Int. J. Oncol. 51 (2017) 281–288. L. Goense, P.S. van Rossum, J.B. Reitsma, M.G. Lam, G.J. Meijer, M. van Vulpen, J.P. Ruurda, R. van Hillegersberg, Diagnostic performance of 18F-FDG PET and PET/CT for the detection of recurrent esophageal Cancer After treatment with curative intent: a systematic review and meta-analysis, J. Nucl. Med. 56 (2015) 995–1002. H.R. Shin, C. Joubert, M. Boniol, C. Hery, S.H. Ahn, Y.J. Won, Y. Nishino, T. Sobue, C.J. Chen, S.L. You, M.R. Mirasol-Lumague, S.C. Law, O. Mang, Y.B. Xiang, K.S. Chia, S. Rattanamongkolgul, J.G. Chen, M.P. Curado, P. Autier, Recent trends and patterns in breast cancer incidence among Eastern and Southeastern Asian women, Cancer Causes Control 21 (2010) 1777–1785. F. Bray, P. McCarron, D.M. Parkin, The changing global patterns of female breast cancer incidence and mortality, Breast Cancer Res. 6 (2004) 229–239. NCCN: Clinical Practice Guidelines in oncology 2016. https://www.nccn.org/ patients/guidelines/stage_i_ii_breast/files/assets/common/downloads/files/ stageibreast.pdf Accessed on Febuary. 26, 2018. K. Kitajima, Y. Miyoshi, Present and future role of FDG-PET/CT imaging in the management of breast cancer, J. Radiol. 34 (2016) 167–180. H.S. Kim, A.Y. Lee, J.E. Jo, B.C. Moon, Y. Ji, H.K. Kim, Optimization of ultrasonicassisted extraction of continentalic acid from the root of Aralia continentalis by using the response surface methodology, Arch. Pharm. Res. 37 (2014) 1437–1444. B. Huang, M.W. Law, P.L. Khong, Whole-body PET/CT scanning: estimation of radiation dose and cancer risk, Radiology 251 (2009) 166–174. G. Brix, U. Lechel, G. Glatting, S.I. Ziegler, W. Münzing, S.P. Müller, T. Beyer, Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations, J. Nucl. Med. 46 (2005) 608–613. L.K. Griffeth, K.M. Rich, F. Dehdashti, J.R. Simpson, M.J. Fusselman, A.H. McGuire, B.A. Siegel, Brain metastases from non-central nervous system tumors: evaluation with PET, Radiology. 186 (1993) 37–44. K. Kitajima, Y. Nakamoto, H. Okizuka, Y. Onishi, M. Senda, N. Suganuma, K. Sugimura, Accuracy of whole-body FDG-PET/CT for detecting brain metastases from non-central nervous system tumors, Ann. Nucl. Med. 22 (2008) 595–602. E.D. Rappeport, A. Loft, A.K. Berthelsen, P. von der Recke, P.N. Larsen, A.M. Mogensen, A. Wettergren, A. Rasmussen, J. Hillingsoe, P. Kirkegaard, C. Thomsen, Contrast-enhanced FDG-PET/CT vs. SPIO-enhanced MRI vs. FDG-PET vs. CT in patients with liver metastases from colorectal cancer: a prospective study with intraoperative confirmation, Acta Radiol. 48 (2007) 369–378. A. Boss, S. Bisdas, A. Kolb, M. Hofmann, U. Ernemann, C.D. Claussen, C. Pfannenberg, B.J. Pichler, M. Reimold, L. Stegger, Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT, J. Nucl. Med. 51 (2010) 1198–1205. A. Boss, L. Stegger, S. Bisdas, A. Kolb, N. Schwenzer, M. Pfister, C.D. Claussen, B.J. Pichler, C. Pfannenberg, Feasibility of simultaneous PET/MR imaging in the head and upper neck area, Eur. Radiol. 21 (2011) 1439–1446. L. Heacock, J. Weissbrot, R. Raad, N. Campbell, K.P. Friedman, F. Ponzo, H. Chandarana, PET/MRI for the evaluation of patients with lymphoma: initial observations, AJR Am. J. Roentgenol. 204 (2015) 842–848. A. Drzezga, M. Souvatzoglou, M. Eiber, A.J. Beer, S. Fürst, A. Martinez-Möller, S.G. Nekolla, S. Ziegler, C. Ganter, E.J. Rummeny, M. Schwaiger, First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses, J. Nucl. Med. 53 (2012) 845–855. C. Buchbender, T.A. Heusner, T.C. Lauenstein, A. Bockisch, G. Antoch, Oncologic PET/MRI, part 2: bone tumors, soft-tissue tumors, melanoma, and lymphoma, J. Nucl. Med. 53 (2012) 1244–1252. C. Buchbender, T.A. Heusner, T.C. Lauenstein, A. Bockisch, G. Antoch, Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen, and pelvis, J. Nucl. Med. 53 (2012) 928–938. M.W. Huellner, P. Appenzeller, F.P. Kuhn, L. Husmann, C.M. Pietsch, I.A. Burger, M. Porto, G. Delso, G.K. von Schulthess, P. Veit-Haibach, Whole-body nonenhanced PET/MR versus PET/CT in the staging and restaging of cancers: preliminary observations, Radiology 273 (2014) 859–869. O.A. Catalano, B.R. Rosen, D.V. Sahani, P.F. Hahn, A.R. Guimaraes, M.G. Vangel, E. Nicolai, A. Soricelli, M. Salvatore, Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients–a hypothesis-generating exploratory study, Radiology 269 (2013) 857–869. S.I. Lee, O.A. Catalano, F. Dehdashti, Evaluation of gynecologic cancer with MR imaging, 18F-FDG PET/CT, and PET/ MR imaging, J. Nucl. Med. 56 (2015) 436–443. Y. Ohno, H. Koyama, H.Y. Lee, T. Yoshikawa, K. Sugimura, Magnetic resonance imaging (MRI) and positron emission tomography (PET)/MRI for lung Cancer Staging, J. Thorac. Imaging 31 (2016) 215–227. K. Beiderwellen, L. Geraldo, V. Ruhlmann, P. Heusch, B. Gomez, F. Nensa, L. Umutlu, T.C. Lauenstein, Accuracy of [18F]FDG PET/MRI for the detection of liver metastases, PLoS ONE 10 (2015) e0137285. C. Giraudo, M. Raderer, G. Karanikas, M. Weber, B. Kiesewetter, W. Dolak, I. Simonitsch-Klupp, M.E. Mayerhoefer, 18F-fluorodeoxyglucose positron emission Tomography/Magnetic resonance in lymphoma: comparison with 18FFluorodeoxyglucose positron emission Tomography/Computed tomography and with the addition of magnetic resonance diffusion-weighted imaging, Invest. Radiol. 51 (2016) 163–169.
European Journal of Radiology 107 (2018) 158–165
C.-Y. Lin et al.
with cervical carcinoma: a metaanalysis, J. Nucl. Med. 51 (2010) 360–367. [57] A.K. Akobeng, Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice, Acta Paediatr. 96 (2007) 487–491. [58] https://clinicaltrials.gov/ct2/show/NCT03510988 Accessed on July, 19th 2018. [59] https://clinicaltrials.gov/ct2/show/NCT03374826?term=PET%2FMRI&cond= Breast+Cancer&rank=4 Accessed on July, 19th 2018.
[55] C. Brendle, N.F. Schwenzer, H. Rempp, H. Schmidt, C. Pfannenberg, C. la Fougère, K. Nikolaou, C. Schraml, Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series, Eur. J. Nucl. Med. Mol. Imaging 43 (2016) 123–132. [56] S. Kang, S.K. Kim, D.C. Chung, S.S. Seo, J.Y. Kim, B.H. Nam, S.Y. Park, Diagnostic value of (18)F-FDG PET for evaluation of paraaortic nodal metastasis in patients
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