Familial Cancer

, Volume 17, Issue 2, pp 287–294 | Cite as

Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic

  • Jasmina Bojadzieva
  • Behrang Amini
  • Suzanne F. Day
  • Tiffiny L. Jackson
  • Parijatham S. Thomas
  • Brandy J. Willis
  • Whitney R. Throckmorton
  • Najat C. Daw
  • Therese B. Bevers
  • Louise C. StrongEmail author
Original Article


Individuals with Li-Fraumeni syndrome (LFS) have a significantly increased lifetime cancer risk affecting multiple organ sites. Therefore, novel comprehensive screening approaches are necessary to improve cancer detection and survival in this population. The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult (≥21 year old) and pediatric (<21 year old) patients were referred to the LEAD clinic by healthcare providers or self-referred and screened at 6 month intervals. During the study period, 63 LFS individuals were seen in the LEAD clinic including 49 adults (11 male, 38 female) and 14 children (7 male, 7 female). Fifty-three of 63 potentially eligible individuals underwent baseline WB-MRI (41 adults and 12 children) with primary tumors detected in six patients, tumor recurrence in one patient and cancer metastases in one patient. Thirty-five of 63 patients (24 adults and 11 children) underwent baseline brain MRI with primary brain tumors detected in three individuals, also noted on subsequent WB-MRI scans. Three additional tumors were diagnosed that in retrospect review were missed on the initial scan (false negatives) and one tumor noted, but not followed up clinically, was prospectively found to be malignant. The high incidence of asymptomatic tumors identified in this initial screening (13%), supports the inclusion of WB-MRI and brain MRI in the clinical management of individuals with LFS.


Whole body MRI Cancer screening Li-Fraumeni syndrome TP53 LEAD clinic 



We would like to thank Michelle Jackson, MS, CGC and Jessica Profato-Partlow, MS, CGC for their help in setting up the LEAD clinic and coordinating the initial patient visits.


We are very grateful to the Ann Parsons Endowment for Pediatric Genetics for providing funding to Louise C. Strong for the LFS research program including data collection for this report.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10689_2017_34_MOESM1_ESM.pdf (212 kb)
Supplementary material 1 (PDF 212 KB)


  1. 1.
    Li FP, Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71(4):747–752CrossRefPubMedGoogle Scholar
  2. 2.
    Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90(8):606–611CrossRefPubMedGoogle Scholar
  3. 3.
    Bougeard G, Renaux-Petel M, Flaman JM, Charbonnier C, Fermey P, Belotti M, Gauthier-Villars M, Stoppa-Lyonnet D, Consolino E, Brugieres L, Caron O, Benusiglio PR, Bressac-de Paillerets B, Bonadona V, Bonaiti-Pellie C, Tinat J, Baert-Desurmont S, Frebourg T (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33(21):2345–2352. doi: 10.1200/JCO.2014.59.5728 CrossRefPubMedGoogle Scholar
  4. 4.
    Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, Bremer RC, Rosenberg PS, Savage SA (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. doi: 10.1002/cncr.30248 Google Scholar
  5. 5.
    Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA et al (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250(4985):1233–1238CrossRefPubMedGoogle Scholar
  6. 6.
    Nogueira ST, Lima EN, Nobrega AF, Torres Ido C, Cavicchioli M, Hainaut P, Achatz MI (2015) (18)F-FDG PET-CT for surveillance of Brazilian patients with Li-Fraumeni syndrome. Front Oncol 5:38. doi: 10.3389/fonc.2015.00038 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Masciari S, Van den Abbeele AD, Diller LR, Rastarhuyeva I, Yap J, Schneider K, Digianni L, Li FP, Fraumeni JF Jr, Syngal S, Garber JE (2008) F18-fluorodeoxyglucose-positron emission tomography/computed tomography screening in Li-Fraumeni syndrome. JAMA 299(11):1315–1319. doi: 10.1001/jama.299.11.1315 CrossRefPubMedGoogle Scholar
  8. 8.
    Kleinerman RA (2009) Radiation-sensitive genetically susceptible pediatric sub-populations. Pediatr Radiol 39(Suppl 1):S27–S31. doi: 10.1007/s00247-008-1015-6 Google Scholar
  9. 9.
    Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43(4):289–294. doi: 10.1136/jmg.2005.036319 CrossRefPubMedGoogle Scholar
  10. 10.
    Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu MC, Marsiglia H, Bourgier C (2010) Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 5:104. doi: 10.1186/1748-717X-5-104 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12(6):559–567. doi: 10.1016/S1470-2045(11)70119-X CrossRefPubMedGoogle Scholar
  12. 12.
    Saya S, Killick E, Thomas S, Taylor N, Bancroft EK, Rothwell J, Benafif S, Dias A, Mikropoulos C, Pope J, Chamberlain A, Gunapala R, Committee SSS, Izatt L, Side L, Walker L, Tomkins S, Cook J, Barwell J, Wiles V, Limb L, Eccles D, Leach MO, Shanley S, Gilbert FJ, Hanson H, Gallagher D, Rajashanker B, Whitehouse RW, Koh DM, Sohaib SA, Evans DG, Eeles RA (2017) Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls. Familial Cancer. doi: 10.1007/s10689-017-9965-1 PubMedPubMedCentralGoogle Scholar
  13. 13.
    Chavhan GB, Babyn PS (2011) Whole-body MR imaging in children: principles, technique, current applications, and future directions. Radiographics 31(6):1757–1772. doi: 10.1148/rg.316115523 CrossRefPubMedGoogle Scholar
  14. 14.
    Nievelstein RA, Littooij AS (2016) Whole-body MRI in paediatric oncology. Radiol Med 121(5):442–453. doi: 10.1007/s11547-015-0600-7 CrossRefPubMedGoogle Scholar
  15. 15.
    Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, Gallinger B, Naumer A, Kohlmann W, Novokmet A, Tabori U, Tijerin M, Greer ML, Finlay JL, Schiffman JD, Malkin D (2016) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 17(9):1295–1305. doi: 10.1016/S1470-2045(16)30249-2 CrossRefPubMedGoogle Scholar
  16. 16.
    Cieszanowski A, Maj E, Kulisiewicz P, Grudzinski IP, Jakoniuk-Glodala K, Chlipala-Nitek I, Kaczynski B, Rowinski O (2014) Non-contrast-enhanced whole-body magnetic resonance imaging in the general population: the incidence of abnormal findings in patients 50 years old and younger compared to older subjects. PLoS ONE 9(9):e107840. doi: 10.1371/journal.pone.0107840 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ulus S, Suleyman E, Ozcan UA, Karaarslan E (2016) Whole-body MRI screening in asymptomatic subjects; preliminary experience and long-term follow-up findings. Pol J Radiol 81:407–414. doi: 10.12659/PJR.897570 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Anupindi SA, Bedoya MA, Lindell RB, Rambhatla SJ, Zelley K, Nichols KE, Chauvin NA (2015) Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. Am J Roentgenol 205(2):400–408. doi: 10.2214/AJR.14.13663 CrossRefGoogle Scholar
  19. 19.
    Jhaveri AP, Bale A, Lovick N, Zuckerman K, Deshpande H, Rath K, Schwartz P, Hofstatter EW (2015) The benefit and burden of cancer screening in Li-Fraumeni syndrome: a case report. Yale J Biol Med 88(2):181–185PubMedPubMedCentralGoogle Scholar
  20. 20.
    McBride KA, Ballinger ML, Schlub TE, Young MA, Tattersall MH, Kirk J, Eeles R, Killick E, Walker LG, Shanley S, Thomas DM, Mitchell G (2017) Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial? Familial Cancer. doi: 10.1007/s10689-016-9964-7 PubMedGoogle Scholar
  21. 21.
    Ross J, Bojadzieva J, Peterson S, Noblin SJ, Yzquierdo R, Askins M, Strong L (2017) The psychosocial effects of the Li-Fraumeni Education and Early Detection (LEAD) program on individuals with Li-Fraumeni syndrome. Genet Med. doi: 10.1038/gim.2017.8 PubMedPubMedCentralGoogle Scholar
  22. 22.
    Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomark Prev 10(2):83–87Google Scholar
  23. 23.
    Mai PL, Malkin D, Garber JE, Schiffman JD, Weitzel JN, Strong LC, Wyss O, Locke L, Means V, Achatz MI, Hainaut P, Frebourg T, Evans DG, Bleiker E, Patenaude A, Schneider K, Wilfond B, Peters JA, Hwang PM, Ford J, Tabori U, Ognjanovic S, Dennis PA, Wentzensen IM, Greene MH, Fraumeni JF Jr, Savage SA (2012) Li-Fraumeni syndrome: report of a clinical research workshop and creation of a research consortium. Cancer Genet 205(10):479–487. doi: 10.1016/j.cancergen.2012.06.008 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ballinger ML, Best A, Mai PL, Khincha PP, Loud JT, Peters JA, Achatz MI, Chojniak R, Balieiro da Costa A, Santiago KM, Garber J, O’Neill AF, Eeles RA, Evans DG, Bleiker E, Sonke GS, Ruijs M, Loo C, Schiffman J, Naumer A, Kohlmann W, Strong LC, Bojadzieva J, Malkin D, Rednam SP, Stoffel EM, Koeppe E, Weitzel JN, Slavin TP, Nehoray B, Robson M, Walsh M, Manelli L, Villani A, Thomas DM, Savage SA (2017) Baseline surveillance in Li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol. doi: 10.1001/jamaoncol.2017.1968 Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Jasmina Bojadzieva
    • 1
  • Behrang Amini
    • 2
  • Suzanne F. Day
    • 3
  • Tiffiny L. Jackson
    • 3
  • Parijatham S. Thomas
    • 3
  • Brandy J. Willis
    • 4
  • Whitney R. Throckmorton
    • 5
  • Najat C. Daw
    • 5
  • Therese B. Bevers
    • 3
  • Louise C. Strong
    • 1
    Email author
  1. 1.Department of GeneticsThe University of Texas MD Anderson CancerHoustonUSA
  2. 2.Department of Diagnostic RadiologyThe University of Texas MD Anderson CancerHoustonUSA
  3. 3.Department of Cancer PreventionThe University of Texas MD Anderson CancerHoustonUSA
  4. 4.Department of Imaging PhysicsThe University of Texas MD Anderson CancerHoustonUSA
  5. 5.Department of PediatricsMD Anderson CancerHoustonUSA

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