Dataset Information

Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis.

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.

SUBMITTER: Ballinger ML

PROVIDER: S-EPMC5824277 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis.

Ballinger Mandy L ML Best Ana A Mai Phuong L PL Khincha Payal P PP Loud Jennifer T JT Peters June A JA Achatz Maria Isabel MI Chojniak Rubens R Balieiro da Costa Alexandre A Santiago Karina Miranda KM Garber Judy J O'Neill Allison F AF Eeles Rosalind A RA Evans D Gareth DG Bleiker Eveline E Sonke Gabe S GS Ruijs Marielle M Loo Claudette C Schiffman Joshua J Naumer Anne A Kohlmann Wendy W Strong Louise C LC Bojadzieva Jasmina J Malkin David D Rednam Surya P SP Stoffel Elena M EM Koeppe Erika E Weitzel Jeffrey N JN Slavin Thomas P TP Nehoray Bita B Robson Mark M Walsh Michael M Manelli Lorenzo L Villani Anita A Thomas David M DM Savage Sharon A SA

JAMA oncology 20171201 12

<h4>Importance</h4>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.<h4>Objective</h4>To assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline.<h4>Data sources</h4>Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium.<h4>Study ...[more]

PMID: 28772291

Similar Datasets

Project description:ImportanceEstablishment of an optimal cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with Li-Fraumeni syndrome, a rare, highly penetrant cancer predisposition syndrome.ObjectiveTo determine the feasibility and efficacy of a comprehensive cancer screening regimen in Li-Fraumeni syndrome, using multiple radiologic techniques, including rapid whole-body magnetic resonance imaging (MRI) and laboratory measurements.Design, setting, and participantsBaseline evaluation of a prospective cancer screening study was conducted from June 1, 2012, to July 30, 2016, at the National Cancer Institute, National Institutes of Health (an academic research facility). Participants included 116 individuals with Li-Fraumeni syndrome with a germline TP53 pathogenic variant who were aged 3 years or older at the time of baseline screening and had not received active cancer therapy at least 6 months prior to screening.Main outcomes and measuresDetection of prevalent cancer with multimodal screening techniques and the need for additional evaluation.ResultsOf the 116 study participants, 77 (66.4%) were female; median age was 37.6 years (range, 3-68 years). Baseline cancer screening led to the diagnosis of cancer in 8 (6.9%) individuals (2 lung adenocarcinomas, 1 osteosarcoma, 1 sarcoma, 1 astrocytoma, 1 low-grade glioma, and 2 preinvasive breast cancers [ductal carcinoma in situ]); all but 1 required only resection for definitive treatment. A total of 40 (34.5%) participants required additional studies to further investigate abnormalities identified on screening, with 32 having incidental, benign, or normal findings, resulting in a false-positive rate of 29.6%. Non-MRI techniques, including baseline blood tests, abdominal ultrasonography in children, mammography, and colonoscopy, did not lead to a diagnosis of prevalent cancer in our cohort.Conclusions and relevanceThis study describes the establishment and feasibility of an intensive cancer surveillance protocol for individuals with Li-Fraumeni syndrome. Prevalent cancers were detected at an early stage with baseline whole-body, brain, and breast MRI. Prospective screening of the participants is under way.

Project description:BackgroundIn Brazil, there is a higher prevalence of Li-Fraumeni Syndrome (LFS) compared to worldwide, due to the founder mutation in the TP53 gene p.R337H. However, a large portion of the population, that depends on National Health Care System, does not have access to effective screening through the Toronto Protocol guidelines that enables early diagnosis and improves overall survival. Population strategies for early cancer detection recommended in Brazil are limited and additional screening is not offered to patients at a high risk, leading to late diagnoses and higher cancer mortality. This study aims to assess the cost-effectiveness of introducing annual screening that follows the Toronto Protocol for patients diagnosed with LFS in Brazil.MethodsA Markov decision analytic model was developed to estimate cost-effectiveness of 1,000 LFS carriers under surveillance and non-surveillance strategies over a patient's lifetime. The main outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per additional life year gained, comparing surveillance and non-surveillance strategies in p.R337H TP53 carriers.FindingsFor females, the model showed a mean cost of $2,222 and $14,640 and yielded 22 and 26·2 life years for non-surveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $2,982 per additional life year gained. For males, the model predicts mean lifetime costs of $1,165 and $12,883 and average life years of 23·5 and 26·3 for non-surveillance and surveillance strategies, respectively. This amounts to an ICER of $ 4,185 per additional life year. Surveillance had 64% and 45% probabilities of being the most cost-effective strategy for early cancer detection in female and male carriers, respectively.InterpretationThe adoption of surveillance for patients diagnosed with LFS by the Brazilian National Health Care System is cost-beneficial for both males and females.FundingThis research received no specific grant from any funding agency.

Project description:IntroductionExperiences of illness change the physical body and embodiments, or the ways in which the world and the self are known through the body. When illness is anticipated, such as with inherited cancer predisposition syndromes, risk becomes embodied and shared in family groups. Embodied risk is experienced whether or not symptoms have manifested. To examine how individuals and families with genetic risk experience the world and understand their disease through their bodies, we employ Li-Fraumeni syndrome (LFS) as an exemplar. LFS is a rare, genetic, cancer predisposition syndrome with nearly 100% lifetime cancer risk starting from birth, limited opportunities for prevention, rigorous screening protocols, and early mortality.MethodsForty-five families, including 117 individuals aged 13-81 years, enrolled in the National Cancer Insitute's LFS study (NCT01443468) completed 66 open-ended interviews regarding LFS experiences. An interdisciplinary team used modified grounded theory to explore physical aspects of living with LFS in psychosocial contexts.FindingsThe physicality of living with LFS included constant monitoring of LFS bodies across the family to identify physical change that might indicate carcinogenesis. Cancer screening, risk reduction, and treatment acted as dually protective and invasive, and as an unavoidable features of LFS. Connections between family members with similar embodiments normalized aesthetic changes and supported coping with visible markers of difference. In some circumstances, participants objectified the body to preserve the self and important relationships. In others, intense pain or loss created thresholds beyond which the self could no longer be separated from the body to support coping.DiscussionThis paper focuses on Li-Fraumeni syndrome, a familial condition with a well-established genetic identity in which the body-self is experienced in relation to important others, to medical imaging, and to historical experiences with cancer. We expand on theories of embodied risk and inter-embodiment to describe experiences across disease trajectories, with attention to division and union between body, self, and other.

Dataset Information

Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets