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Original Investigation
December 2017

Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance ImagingA Meta-analysis

Author Affiliations
  • 1Cancer Division, Garvan Institute of Medical Research, Sydney, Australia
  • 2Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 3Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
  • 4Department of Imaging, A. C. Camargo Cancer Center, São Paulo, Brazil
  • 5Department of Medical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil
  • 6National Institute for Oncogenomics, A. C. Camargo Cancer Center, São Paulo, Brazil
  • 7Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 8Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 9Division of Genetics and Epidemiology, The Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, England
  • 10Department of Genetic Medicine, St Mary’s Hospital, Manchester, England
  • 11Division of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam
  • 12Department of Medical Oncology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam
  • 13Family Cancer Clinic, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam
  • 14Department of Radiology, the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam
  • 15Department of Pediatric Hematology/Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City
  • 16Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston
  • 17Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • 18Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
  • 19Department of Pediatrics, Section of Hematology-Oncology, Texas Children’s Cancer Center, Baylor College of Medicine, Houston
  • 20Department of Internal Medicine, University of Michigan, Ann Arbor
  • 21Division of Clinical Cancer Genetics, City of Hope, Duarte, California
  • 22Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 23Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York
  • 24Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2017;3(12):1634-1639. doi:10.1001/jamaoncol.2017.1968
Key Points

Question  Does baseline whole-body magnetic resonance imaging detect asymptomatic cancers at a curable stage in germline TP53 mutation carriers?

Findings  In a meta-analysis of 13 cohorts that included 578 participants, the estimated overall detection rate for previously unrecognized new, localized malignant neoplasms by a single baseline scan in TP53 mutation carriers was 7%, and the false-positive rate was 42.5%. All screen-detected new cancers were treated with curative intent.

Meaning  Baseline evaluation with whole-body magnetic resonance imaging offers important clinical utility in the management of cancer risk in TP53 mutation carriers.

Abstract

Importance  Guidelines for clinical management in Li-Fraumeni syndrome, a multiple-organ cancer predisposition condition, are limited. Whole-body magnetic resonance imaging (WBMRI) may play a role in surveillance of this high-risk population.

Objective  To assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline.

Data Sources  Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium.

Study Selection  Cohorts that incorporated WBMRI for individuals with germline TP53 mutations from January 1, 2004, through October 1, 2016, were included.

Data Extraction and Synthesis  Data were extracted by investigators from each cohort independently and synthesized by 2 investigators. Random-effects meta-analysis methods were used to estimate proportions.

Main Outcomes and Measures  The proportions of participants at baseline in whom a lesion was detected that required follow-up and in whom a new primary malignant neoplasm was detected.

Results  A total of 578 participants (376 female [65.1%] and 202 male [34.9%]; mean [SD] age, 33.2 [17.1] years) from 13 cohorts in 6 countries were included in the analysis. Two hundred twenty-five lesions requiring clinical follow-up were detected by WBMRI in 173 participants. Sixty-one lesions were diagnosed in 54 individuals as benign or malignant neoplasms. Overall, 42 cancers were identified in 39 individuals, with 35 new localized cancers treated with curative intent. The overall estimated detection rate for new, localized primary cancers was 7% (95% CI, 5%-9%).

Conclusions and Relevance  These data suggest clinical utility of baseline WBMRI in TP53 germline mutation carriers and may form an integral part of baseline clinical risk management in this high-risk population.

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