Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort

Phuong, L.; Khincha, Payal P.; Loud, Jennifer T.; DeCastro, Rosamma; Bremer, Renee; Peters, June A.; Liu, Chia Ying; Bluemke, David A.; Malayeri, Ashkan A.; Savage, Sharon A.

doi:10.1001/jamaoncol.2017.1350

Cited by 51 publications

(40 citation statements)

References 23 publications

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“…This result supports the relevance of annual examinations for LFS patients. These results are also consistent with previous observations that WB-MRI facilitates the early detection of malignant tumors [ 19 , 26 – 28 ]. Low positivity and recall rates were observed, and further investigations of positive results predominantly involved radiological methods.…”

Section: Discussionsupporting

confidence: 93%

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Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients

et al. 2018

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BackgroundLi-Fraumeni syndrome (LFS) is an autosomal dominant disease that is associated with germline TP53 mutations and it predisposes affected individuals to a high risk of developing multiple tumors. In Brazil, LFS is characterized by a different pattern of TP53 variants, with the founder TP53 p.R337H mutation being predominant. The adoption of screening strategies to diagnose LFS in its early stages is a major challenge due to the diverse spectrum of tumors that LFS patients can develop. The purpose of this study was to evaluate two rounds of whole-body magnetic resonance imaging (WB-MRI) which were conducted as a screening strategy for LFS patients.MethodsOver a 4-year period, 59 LFS patients underwent two rounds of WB-MRI. Each MRI was characterized as positive or negative, and positive cases were further investigated to establish a diagnosis. The parameters used to evaluate the WB-MRI results included: positive rate, number of invasive investigations of positive results, and cancer detection rate.ResultsA total of 118 WB-MRI scans were performed. Positive results were associated with 11 patients (9.3%). Seven of these patients (11.8%) were identified in the first round of screening and 4 patients (6.7%) were identified in the second round of screening. Biopsies were performed in three cases (2.5%), two (3.4%) after the first round of screening and one (1.7%) after the second round of screening. The histopathological results confirmed a diagnosis of cancer for all three cases. There was no indication of unnecessary invasive procedures.ConclusionsWB-MRI screening of LFS carriers diagnosed cancers in their early stages. When needed, positive results were further examined with non-invasive imaging techniques. False positive results were less frequent after the first round of WB-MRI screening.Electronic supplementary materialThe online version of this article (10.1186/s40644-018-0162-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

“…In 2017, Mai et al [ 28 ] also evaluated a screening protocol that included WB-MRI for examining 116 patients of a National Cancer Institute (NCI) Li-Fraumeni cohort. In this baseline screening, cancers were detected in 6.9% of the cohort, and 34.5% of these lesions required further investigation.…”

Section: Introductionmentioning

confidence: 99%

Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients

et al. 2018

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“…The cumulative risks of breast and ovarian cancers in BRCA1/2 mutation carriers are reported to be 72% (95% confidence interval [CI], 65 to 79) and 44% (95% CI, 36 to 53), respectively, in BRCA1 carriers and 69% (95% CI, 61 to 77) and 17% (95% CI, 11 to 25), respectively, in BRCA2 carriers [1]. The cumulative cancer risk associated with TP53 mutation may be as high as 90% by the age of 60 years [2]. In addition to mutations in BRCA1/2 and TP53, germline mutations in certain genes were associated with more than 50 hereditary cancer syndromes.…”

Section: Introductionmentioning

confidence: 99%

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

et al. 2020

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PurposeHereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).Materials and MethodsA total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.ResultsOf 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.ConclusionNGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

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“…If cancer surveillance does indeed detect a greater frequency of tumors that are treated as compared with what would normally be treated (i.e., unrecognized overdiagnosis of nonmalignant lesions leading to possible overtreatment), this could render the strategy less cost‐effective. However, recent analyses among patients with LFS have found that overdiagnosis and unnecessary treatment of indolent lesions to be uncommon . Additional estimates of tumor development and patient survival using real‐world data are needed to determine the likelihood of this occurring.…”

Section: Discussionmentioning

confidence: 99%

Cost‐effectiveness of early cancer surveillance for patients with Li–Fraumeni syndrome

Tak

Biltaji

Kohlmann

et al. 2019

Pediatric Blood & Cancer

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Introduction Patients with germline TP53 pathogenic variants (Li–Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost‐effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. Methods A Markov decision analytic model was developed from a third‐party payer perspective to estimate cost‐effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post‐cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost‐effectiveness ratio (ICER; change in cost/LY gained). One‐way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. Results The model showed a mean cost of $46 496 and $117 102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17 125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100 000/life‐year gained, surveillance had a 98% probability of being the most cost‐effective strategy for early cancer detection in this high‐risk population. Conclusions Presymptomatic cancer surveillance is cost‐effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.

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Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort

Cited by 51 publications

References 23 publications

Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients

Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

Cost‐effectiveness of early cancer surveillance for patients with Li–Fraumeni syndrome

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