European Radiology

, Volume 22, Issue 1, pp 26–38 | Cite as

Magnetic resonance imaging in the preoperative assessment of patients with primary breast cancer: systematic review of diagnostic accuracy and meta-analysis

  • María Nieves Plana
  • Carmen Carreira
  • Alfonso Muriel
  • Miguel Chiva
  • Víctor Abraira
  • Jose Ignacio Emparanza
  • Xavier Bonfill
  • Javier Zamora
Breast

Abstract

Objectives

To estimate the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting additional lesions and contralateral cancer not identified using conventional imaging in primary breast cancer.

Methods

We have conducted a systematic review and meta-analyses to estimate diagnostic accuracy indices and the impact of MRI on surgical management.

Results

Fifty articles were included (n = 10,811 women). MRI detected additional disease in 20% of women and in the contralateral breast in 5.5%. The summary PPV of ipsilateral additional disease was 67% (95% CI 59–74%). For contralateral breast, the PPV was 37% (95% CI 27–47%). For ipsilateral lesions, MRI devices ≥1.5 Tesla (T) had higher PPV (75%, 95% CI 64–83%) than MRI with <1.5 T (59%, 95% CI 53–71%). Similar results were found for contralateral cancer, PPV 40% (95% CI 29–53%) and 19% (95% CI 8–39%) for high- and low-field equipments, respectively. True positive MRI findings prompted conversion from wide local excision (WLE) to more extensive surgery in 12.8% of women while in 6.3% this conversion was inappropriate.

Conclusions

MRI shows high diagnostic accuracy, but MRI findings should be pathologically verified because of the high FP rate. Future research on this emerging technology should focus on patient outcome as the primary end-point.

Key Points

• Breast Magnetic Resonance Imaging is becoming increasingly popular for cancer staging before surgery.

• This diagnostic accuracy systematic review and meta-analysis updates previous ones demonstrating MRI has high diagnostic accuracy and causes more extensive surgery.

• Magnetic Resonance protocols at 1.5 T or greater shows greater positive predictive value than lower-field equipments.

• The actual impact on clinical relevant outcomes should be addressed with properly designed randomized controlled trials.

Keywords

Breast cancer Magnetic resonance imaging Sensitivity and specificity Systematic review Meta-analysis 

References

  1. 1.
    Sardanelli F, Boetes C, Borisch B, Decker T, Federico M, Gilbert FJ, Helbich T, Heywang-Kobrunner SH, Kaiser WA, Kerin MJ, Mansel RE, Marotti L, Martincich L, Mauriac L, Meijers-Heijboer H, Orecchia R, Panizza P, Ponti A, Purushotham AD, Regitnig P, Del Turco MR, Thibault F, Wilson R (2010) Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer 46:1296–1316PubMedCrossRefGoogle Scholar
  2. 2.
    Sardanelli F (2010) Additional findings at preoperative MRI: a simple golden rule for a complex problem? Breast Cancer Res Treat 124:717–721PubMedCrossRefGoogle Scholar
  3. 3.
    Orel S (2008) Who should have breast magnetic resonance imaging evaluation? J Clin Oncol 26(5):703–711PubMedCrossRefGoogle Scholar
  4. 4.
    Berg WA, Gutierrez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS, Ioffe OB (2004) Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 233:830–849PubMedCrossRefGoogle Scholar
  5. 5.
    Boetes C, Mus RD, Holland R, Barentsz JO, Strijk SP, Wobbes T, Hendriks JH, Ruys SH (1995) Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent. Radiology 197:743–747PubMedGoogle Scholar
  6. 6.
    Fischer U, Kopka L, Grabbe E (1999) Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the therapeutic approach. Radiology 213:881–888PubMedGoogle Scholar
  7. 7.
    Mumtaz H, Hall-Craggs MA, Davidson T, Walmsley K, Thurell W, Kissin MW, Taylor I (1997) Staging of symptomatic primary breast cancer with MR imaging. Am J Roentgenol 169(2):417–24Google Scholar
  8. 8.
    Solin LJ (2010) Counterview: pre-operative breast MRI (magnetic resonance imaging) is not recommended for all patients with newly diagnosed breast cancer. Breast 19:7–9PubMedCrossRefGoogle Scholar
  9. 9.
    Houssami N, Ciatto S, Macaskill P, Lord SJ, Warren RM, Dixon JM, Irwig L (2008) Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol 26:3248–3258PubMedCrossRefGoogle Scholar
  10. 10.
    Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, Peacock S, Smazal SF, Maki DD, Julian TB, DePeri ER, Bluemke DA, Schnall MD, ACRIN T (2007) MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 356:1295–1303PubMedCrossRefGoogle Scholar
  11. 11.
    Brennan ME, Houssami N, Lord S, Macaskill P, Irwig L, Dixon JM, Warren RM, Ciatto S (2009) Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: systematic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol 27:5640–5649PubMedCrossRefGoogle Scholar
  12. 12.
    Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25PubMedCrossRefGoogle Scholar
  13. 13.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRefGoogle Scholar
  14. 14.
    Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–93PubMedCrossRefGoogle Scholar
  15. 15.
    Zamora J, Abraira V, Muriel A, Khan KS, Coomarasamy A (2006) Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 6:31PubMedCrossRefGoogle Scholar
  16. 16.
    Harbord RM (2008) Metandi:Stata module for meta-analysis of diagnostic accuracy. Statistical Software Components, Boston College Department of Economics. Revised 15 Apr 2008Google Scholar
  17. 17.
    SAS Institute: SAS/STAT User’s Guide, version 9.1. (Cary (NC):SAS Institute, 1999). 2010Google Scholar
  18. 18.
    Martinez V, Carreira C, Pérez Y, Moreno A, Ramírez M, Chiva M, Miranda P (2007) Effect of preoperative magnetic resonance imaging on the surgical treatment of breast carcinoma. Prog Obstet Ginecol 50:682–688CrossRefGoogle Scholar
  19. 19.
    Olivas-Maguregui S, Villasenor-Navarro Y, Ferrari-Carballo T, Morales-Chairez V, Michel-Ortega RM, Ceron-Lizarraga T, Silva-Godinez JC, Arrieta O (2008) Importance of the preoperative evaluation of multifocal and multicentric breast cancer with magnetic resonance imaging in women with dense parenchyma. Rev Invest Clin 60:382–389PubMedGoogle Scholar
  20. 20.
    Tan JE, Orel SG, Schnall MD, Schultz DJ, Solin LJ (1999) Role of magnetic resonance imaging and magnetic resonance imaging–guided surgery in the evaluation of patients with early-stage breast cancer for breast conservation treatment. Am J Clin Oncol 22:414–418PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang Y, Fukatsu H, Naganawa S, Satake H, Sato Y, Ohiwa M, Endo T, Ichihara S, Ishigaki T (2002) The role of contrast-enhanced MR mammography for determining candidates for breast conservation surgery. Breast Cancer 9:231–239PubMedCrossRefGoogle Scholar
  22. 22.
    Pediconi F, Venditti F, Padula S, Roselli A, Moriconi E, Giacomelli L, Catalano C, Passariello R (2005) CE-Magnetic Resonance Mammography for the evaluation of the contralateral breast in patients with diagnosed breast cancer. Radiol Med (Torino) 110:61–68Google Scholar
  23. 23.
    Dao TN, Lamont JP, Knox SM (2007) Clinical utility of breast magnetic resonance imaging in patients presenting with primary breast cancer. Baylor University Medical Center Proceedings 20:227–230PubMedGoogle Scholar
  24. 24.
    Furman B, Gardner MS, Romilly P, Clark J, Stowell N, Green B, Ebert M, Patel A, Cox C (2003) Effect of 0.5 Tesla magnetic resonance imaging on the surgical management of breast cancer patients. Am J Surg 186:344–347PubMedCrossRefGoogle Scholar
  25. 25.
    Orel SG, Schnall MD, Powell CM, Hochman MG, Solin LJ, Fowble BL, Torosian MH, Rosato EF (1995) Staging of suspected breast cancer: effect of MR imaging and MR-guided biopsy. Radiology 196(1):115–122PubMedGoogle Scholar
  26. 26.
    Upponi SS, Warren RML (2006) The diagnostic impact of contrast-enhanced MRI in management of breast disease. Breast 15(6):736–743PubMedCrossRefGoogle Scholar
  27. 27.
    Van GM, Schelfout K, Dijckmans L, Van der Auwera JC, Weyler J, Verslegers I, Biltjes I, De SA (2004) MR mammography in the pre-operative staging of breast cancer in patients with dense breast tissue: comparison with mammography and ultrasound. Eur Radiol 14:809–816CrossRefGoogle Scholar
  28. 28.
    Scomersi S, Urbani M, Tonutti M, Zanconati F, Bortul M (2010) Role of magnetic resonance imaging in managing selected women with newly diagnosed breast cancer. Breast 19:115–119PubMedCrossRefGoogle Scholar
  29. 29.
    Sardanelli F, Giuseppetti GM, Panizza P, Bazzocchi M, Fausto A, Simonetti G, Lattanzio V, Del MA, Italian Trial for Breast MR in Multifocal/Multicentric Cancer (2004) Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer in Fatty and dense breasts using the whole-breast pathologic examination as a gold standard. Am J Roentgenol 183(4):1149–57Google Scholar
  30. 30.
    Fischer U, Vosshenrich R, Probst A, Burchhardt H, Grabbe E (1994) Preoperative MR mammography in patients with breast cancer—Useful information or useless extravagance? 161(4):300–306Google Scholar
  31. 31.
    Gatzemeier W, Liersch T, Stylianou A, Buttler A, Becker H, Fischer U (1999) Preoperative MR mammography in breast carcinoma. Effect on operative treatment from the surgical viewpoint. Chirurg 70:1460–1468PubMedCrossRefGoogle Scholar
  32. 32.
    Braun M, Polcher M, Schrading S, Zivanovic O, Kowalski T, Flucke U, Leutner C, Park-Simon TW, Rudlowski C, Kuhn W, Kuhl CK (2008) Influence of preoperative MRI on the surgical management of patients with operable breast cancer. Breast Canc Res Treat 111:179–187CrossRefGoogle Scholar
  33. 33.
    Turnbull L, Brown S, Harvey I, Olivier C, Drew P, Napp V, Hanby A, Brown J (2010) Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 375:563–571PubMedCrossRefGoogle Scholar
  34. 34.
    Liberman L, Morris EA, Kim CM, Kaplan JB, Abramson AF, Menell JH, Van Zee KJ, Dershaw DD (2003) MR imaging findings in the contralateral breast of women with recently diagnosed breast cancer. Am J Roentgenol 180(2):333–41Google Scholar
  35. 35.
    Lehman CD, Blume JD, Thickman D, Bluemke DA, Pisano E, Kuhl C, Julian TB, Hylton N, Weatherall P, O’Loughlin M, Schnitt SJ, Gatsonis C, Schnall MD (2005) Added cancer yield of MRI in screening the contralateral breast of women recently diagnosed with breast cancer: results from the International Breast Magnetic Resonance Consortium (IBMC) trial. J Surg Oncol 92:9–15PubMedCrossRefGoogle Scholar
  36. 36.
    Adkisson CD, Vallow LA, Kowalchik K, McNeil R, Hines S, Deperi E, Moreno A, Roy V, Perez EA, McLaughlin SA (2011) Patient age and preoperative breast MRI in women with breast cancer: biopsy and surgical implications. Ann Surg Oncol 18:1678–1683PubMedCrossRefGoogle Scholar
  37. 37.
    Pettit K, Swatske ME, Gao F, Salavaggione L, Gillanders WE, Aft RL, Monsees BS, Eberlein TJ, Margenthaler JA (2009) The impact of breast MRI on surgical decision-making: are patients at risk for mastectomy? J Surg Oncol 100:553–558PubMedCrossRefGoogle Scholar
  38. 38.
    Lijmer JG, Mol BW, Heisterkamp S, Bonsel GJ, Prins MH, van der Meulen JH, Bossuyt PM (1999) Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 282:1061–1066PubMedCrossRefGoogle Scholar
  39. 39.
    Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG (2003) The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Ann Intern Med 138:W1–12PubMedGoogle Scholar
  40. 40.
    Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC (2003) Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Ann Intern Med 138:40–44PubMedGoogle Scholar
  41. 41.
    Warren R, Ciatto S, Macaskill P, Black R, Houssami N (2009) Technical aspects of breast MRI–do they affect outcomes? Eur Radiol 19:1629–1638PubMedCrossRefGoogle Scholar
  42. 42.
    Al-Hallaq HA, Mell LK, Bradley JA, Chen LF, Ali AN, Weichselbaum RR, Newstead GM, Chmura SJ (2008) Magnetic resonance imaging identifies multifocal and multicentric disease in breast cancer patients who are eligible for partial breast irradiation. Cancer 113:2408–2414PubMedCrossRefGoogle Scholar
  43. 43.
    Bagley FH, Sutton J (2004) The role of magnetic resonance imaging mammography in the surgical management of the index breast cancer. Arch Surg 139(4):380–383PubMedCrossRefGoogle Scholar
  44. 44.
    Bernard JR Jr, Vallow LA, DePeri ER, McNeil RB, Feigel DG, Amar S, Buskirk SJ, Perez EA (2010) In newly diagnosed breast cancer, screening MRI of the contralateral breast detects mammographically occult cancer, even in elderly women: the mayo clinic in Florida experience. Breast J 16:118–126PubMedCrossRefGoogle Scholar
  45. 45.
    Bilimoria KY, Cambic A, Hansen NM, Bethke KP (2007) Evaluating the impact of preoperative breast magnetic resonance imaging on the surgical management of newly diagnosed breast cancers. Arch Surg 142(5):441–445PubMedCrossRefGoogle Scholar
  46. 46.
    Buxant F, Scuotto F, Hottat N, Noel JC, Simon P (2007) Does preoperative magnetic resonance imaging modify breast cancer surgery? Acta Chir Belg 107:288–291PubMedGoogle Scholar
  47. 47.
    Crowe JP, Patrick RJ, Rim A (2009) The importance of preoperative breast MRI for patients newly diagnosed with breast cancer. Breast J 15:52–60PubMedCrossRefGoogle Scholar
  48. 48.
    Cheung Y-C, Wan Y-L, Lo Y-F, Leung W-M, Chen S-C, Hsueh S (2004) Preoperative magnetic resonance imaging evaluation for breast cancers after sonographically guided core-needle biopsy: a comparison study. Ann Surg Oncol 11(8):756–761PubMedCrossRefGoogle Scholar
  49. 49.
    Del FC, Borghese L, Cedolini C, Bestagno A, Puglisi F, Isola M, Soldano F, Bazzocchi M (2007) Role of pre-surgical breast MRI in the management of invasive breast carcinoma. Breast 16:469–481CrossRefGoogle Scholar
  50. 50.
    Deurloo EE, Peterse JL, Rutgers EJ, Besnard AP, Muller SH, Gilhuijs KG (2005) Additional breast lesions in patients eligible for breast-conserving therapy by MRI: impact on preoperative management and potential benefit of computerised analysis. Eur J Cancer 41:1393–1401PubMedCrossRefGoogle Scholar
  51. 51.
    Drew PJ, Chatterjee S, Turnbull LW, Read J, Carleton PJ, Fox JN, Monson JR, Kerin MJ (1999) Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer. Ann Surg Oncol 6:599–603PubMedCrossRefGoogle Scholar
  52. 52.
    Echevarria JJ, Martin M, Saiz A, Imaz I, Fernandez-Ruanova B, Martin D, Lopez-Ruiz JA (2006) Overall breast density in MR mammography: diagnostic and therapeutic implications in breast cancer. J Comput Assist Tomogr 30:140–147PubMedCrossRefGoogle Scholar
  53. 53.
    Elshof LE, Rutgers EJ, Deurloo EE, Loo CE, Wesseling J, Pengel KE, Gilhuijs KG (2010) A practical approach to manage additional lesions at preoperative breast MRI in patients eligible for breast conserving therapy: results. Breast Canc Res Treat 124:707–715CrossRefGoogle Scholar
  54. 54.
    Esserman LJ, Hylton N, Yassa L, Barclay J, Frankel S, Sickles E (1999) Utility of magnetic resonance imaging in the management of breast cancer: evidence for improved preoperative staging. J Clin Oncol 17(1):110–119PubMedGoogle Scholar
  55. 55.
    Hlawatsch A, Teifke A, Schmidt M, Thelen M (2002) Preoperative assessment of breast cancer: sonography versus MR imaging. Am J Roentgenol 179(6):1493–501Google Scholar
  56. 56.
    Hollingsworth AB, Stough RG, O’Dell CA, Brekke CE (2008) Breast magnetic resonance imaging for preoperative locoregional staging. Am J Surg 196:389–397PubMedCrossRefGoogle Scholar
  57. 57.
    Hollingsworth AB, Stough RG (2006) Preoperative breast MRI for locoregional staging. J Okla State Med Assoc 99:505–515PubMedGoogle Scholar
  58. 58.
    Lee SG, Orel SG, Woo IJ, Cruz-Jove E, Putt ME, Solin LJ, Czerniecki BJ, Schnall MD (2003) MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results. Radiology 226:773–778PubMedCrossRefGoogle Scholar
  59. 59.
    Liberman L, Morris EA, Dershaw DD, Abramson AF, Tan LK (2003) MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. Am J Roentgenol 180(4):901–10Google Scholar
  60. 60.
    Lim HI, Choi JH, Yang JH, Han BK, Lee JE, Lee SK, Kim WW, Kim S, Kim JS, Kim JH, Choe JH, Cho EY, Kang SS, Shin JH, Ko EY, Kim SW, Nam SJ (2010) Does pre-operative breast magnetic resonance imaging in addition to mammography and breast ultrasonography change the operative management of breast carcinoma? Breast Canc Res Treat 119:163–167CrossRefGoogle Scholar
  61. 61.
    Mameri CS, Kemp C, Goldman SM, Sobral LA, Ajzen S (2008) Impact of breast MRI on surgical treatment, axillary approach, and systemic therapy for breast cancer. Breast J 14:236–244PubMedCrossRefGoogle Scholar
  62. 62.
    Pediconi F, Catalano C, Padula S, Roselli A, Moriconi E, Dominelli V, Pronio AM, Kirchin MA, Passariello R (2007) Contrast-enhanced magnetic resonance mammography: does it affect surgical decision-making in patients with breast cancer? Breast Canc Res Treat 106:65–74CrossRefGoogle Scholar
  63. 63.
    Pediconi F, Catalano C, Roselli A, Padula S, Altomari F, Moriconi E, Pronio AM, Kirchin MA, Passariello R (2007) Contrast-enhanced MR mammography for evaluation of the contralateral breast in patients with diagnosed unilateral breast cancer or high-risk lesions. Radiology 243:670–680PubMedCrossRefGoogle Scholar
  64. 64.
    Schelfout K, Van GM, Kersschot E, Colpaert C, Schelfhout AM, Leyman P, Verslegers I, Biltjes I, Van den HJ, Gillardin JP, Tjalma W, Van der Auwera JC, Buytaert P, De SA (2004) Contrast-enhanced MR imaging of breast lesions and effect on treatment. Eur J Surg Oncol 30:501–507PubMedCrossRefGoogle Scholar
  65. 65.
    Schell AM, Rosenkranz K, Lewis PJ (2009) Role of breast MRI in the preoperative evaluation of patients with newly diagnosed breast cancer. Am J Roentgenol 192(5):1438–44CrossRefGoogle Scholar
  66. 66.
    Schnall MD, Blume J, Bluemke DA, Deangelis GA, Debruhl N, Harms S, Heywang-Kobrunner SH, Hylton N, Kuhl CK, Pisano ED, Causer P, Schnitt SJ, Smazal SF, Stelling CB, Lehman C, Weatherall PT, Gatsonis CA (2005) MRI detection of distinct incidental cancer in women with primary breast cancer studied in IBMC 6883. J Surg Oncol 92:32–38PubMedCrossRefGoogle Scholar
  67. 67.
    Slanetz PJ, Edmister WB, Yeh ED, Talele AC, Kopans DB (2002) Occult contralateral breast carcinoma incidentally detected by breast magnetic resonance imaging. Breast J 8:145–148PubMedCrossRefGoogle Scholar
  68. 68.
    Kuhl CK, Jost P, Morakkabati N, Zivanovic O, Schild HH, Gieseke J (2006) Contrast-enhanced MR imaging of the breast at 3.0 and 1.5 T in the same patients: initial experience. Radiology 239:666–676PubMedCrossRefGoogle Scholar
  69. 69.
    Pinker K, Grabner G, Bogner W, Gruber S, Szomolanyi P, Trattnig S, Heinz-Peer G, Weber M, Fitzal F, Pluschnig U, Rudas M, Helbich T (2009) A combined high temporal and high spatial resolution 3 Tesla MR imaging protocol for the assessment of breast lesions: initial results. Invest Radiol 44:553–558PubMedCrossRefGoogle Scholar
  70. 70.
    Bogner W, Gruber S, Pinker K, Grabner G, Stadlbauer A, Weber M, Moser E, Helbich TH, Trattnig S (2009) Diffusion-weighted MR for differentiation of breast lesions at 3.0 T: how does selection of diffusion protocols affect diagnosis? Radiology 253:341–351PubMedCrossRefGoogle Scholar
  71. 71.
    Partridge SC, Mullins CD, Kurland BF, Allain MD, DeMartini WB, Eby PR, Lehman CD (2010) Apparent diffusion coefficient values for discriminating benign and malignant breast MRI lesions: effects of lesion type and size. AJR Am J Roentgenol 194:1664–1673PubMedCrossRefGoogle Scholar
  72. 72.
    Ei Khouli RH, Jacobs MA, Mezban SD, Huang P, Kamel IR, Macura KJ, Bluemke DA (2010) Diffusion-weighted imaging improves the diagnostic accuracy of conventional 3.0-T breast MR imaging. Radiology 256:64–73PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2011

Authors and Affiliations

  • María Nieves Plana
    • 1
  • Carmen Carreira
    • 2
  • Alfonso Muriel
    • 1
  • Miguel Chiva
    • 2
  • Víctor Abraira
    • 1
  • Jose Ignacio Emparanza
    • 3
  • Xavier Bonfill
    • 4
  • Javier Zamora
    • 1
  1. 1.Clinical Biostatistics Unit. Hospital Universitario Ramón y Cajal, CIBER en Epidemiología y Salud Pública (CIBERESP) and Instituto de Investigación Sanitaria (IRYCIS)MadridSpain
  2. 2.Servicio de Diagnóstico por ImagenHospital de FuenlabradaMadridSpain
  3. 3.Clinical Epidemiology Unit. CASPe, CIBER-ESPHospital DonostiaSan SebastiánSpain
  4. 4.Iberoamerican Cochrane Centre, Clinical Epidemiology and Public Health Department, CIBER-ESPHospital de la Santa Creu i Sant PauBarcelonaSpain

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