Screening with whole‐body magnetic resonance imaging in pediatric subjects with Li–Fraumeni syndrome: A single institution pilot study

O’Neill, Allison F.; Voss, Stephan D.; Jagannathan, Jyothi P.; Kamihara, Junne; Nibecker, Callie; Itriago-Araujo, Elena; Masciari, Serena; Parker, Erin; Barreto, Maurício Lima; London, Wendy B.; Garber, Judy E.; Diller, Lisa

doi:10.1002/pbc.26822

Cited by 28 publications

(33 citation statements)

References 22 publications

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“…Although this and the expansion of Medicaid have significantly provided greater access to patients in need of cancer screening, many coverage gaps remain . Thus, some patients, such as those with LFS, continue to face financial obstacles to clinically important cancer screening . Moody, in his editorial to JAMA in 1903, emphasized the importance of disease prevention, declaring that no subject “can be more important to the welfare of humanity.” Clinical and reimbursement decision makers need to carefully consider the added costs and benefits to the implementation of clinical surveillance programs and the impact these decisions, including the corresponding cost‐sharing requirements, have on patient care and outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…34,35 Thus, some patients, such as those with LFS, continue to face financial obstacles to clinically important cancer screening. 9,36 Moody, in his editorial to JAMA in 1903, emphasized the importance of disease prevention, declaring that no subject "can be more important to the welfare of humanity." 37 The model we developed has a number of strengths.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Current LFS standard screening protocols 26 have been instituted in clinics throughout the world [27][28][29][30][31] . At MDACC, the Li-Fraumeni Education and Early Detection (LEAD) Program consists of "a centralized approach to patient management, screening exams performed at the same institution, including whole-body MRI and brain MRI, using same technique and same machines enabling more consistent comparison of findings between and across interval exams in patients and a multidisciplinary team that reviews all findings and patient issues to develop follow up recommendations" 29 .…”

Section: Discussionmentioning

confidence: 99%

Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts

Shin

Dodd

Peng

et al. 2019

Preprint

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Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses. An accurate estimation of the penetrance of different cancer types in LFS is crucial to improve the clinical characterization and management of high-risk individuals of LFS. Our competing risk-based statistical model incorporates the pedigree structure efficiently into the penetrance estimation and corrects for the ascertainment bias. A set of TP53 penetrance for three cancer types (breast, BR/sarcoma, SA/others, OT) involved in LFS is then estimated from 186 pediatric-sarcoma families collected at MD Anderson Cancer Center. The penetrance was then validated on a mixed cohort of clinically ascertained families with cancer (total number of families=668). The age-dependent onset probability distributions of specific cancer types are different. For breast cancer, the TP53 penetrance goes up at an earlier age than the reported BRCA1/2 penetrance. We validated the prediction performance of the penetrance estimates via two independent cohorts combined (BR=85, SA=540, OT=158).We obtained areas under the ROC curves (AUCs) of 0.92 (BR), 0.75 (SA), and 0.81 (OT). Our R package, LFSPRO, provides risk estimates for the diagnosis of breast cancer, sarcoma, other cancers or death before cancer diagnosis in future.Significance: Cancer-specific penetrance can facilitate clinical characterization of LFS and will contribute to the management of families at high risk of LFS.

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“…Most recently, improved long‐term survival in TP53 mutation carriers was associated with early tumor detection via intensive surveillance . Several groups internationally are investigating whole‐body MRI in TP53 mutation carriers . A meta‐analysis of whole‐body MRI data including 578 participants from 13 cohorts across six countries estimated an overall detection rate for new localized primary cancers as 7% (95% CI 5%‐9%) at baseline, several of which were sarcomas .…”

Section: Surveillance In Hereditary Sarcomamentioning

confidence: 99%

Translating genomic risk into an early detection strategy for sarcoma

Ballinger

Pinese

Thomas

2018

Genes Chromosomes & Cancer

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Sarcomas have a strong genetic etiology, and the study of families affected by sarcomas has informed much of what we now understand of modern cancer biology. The recent emergence of powerful genetic technologies has led to astonishing reductions in costs and increased throughput. In the clinic, these technologies are revealing a previously unappreciated and rich landscape of genetic cancer risk. In addition to both known and new cancer risk mutations, genomic tools are cataloguing complex and polygenic risk patterns, collectively explaining between 15–25% of apparently sporadic sarcoma cases. The impact on clinical management is exemplified by Li‐Fraumeni Syndrome, the most penetrant sarcoma syndrome. Whole body magnetic resonance imaging can identify surgically resectable cancers in up to one in ten individuals with Li‐Fraumeni Syndrome. Taken together, parallel developments in genomics, therapeutics and imaging technologies will drive closer engagement between genetics and multidisciplinary care of the sarcoma patient in the 21st century.

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Screening with whole‐body magnetic resonance imaging in pediatric subjects with Li–Fraumeni syndrome: A single institution pilot study

Cited by 28 publications

References 22 publications

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

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

Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts

Translating genomic risk into an early detection strategy for sarcoma

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