Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma

Eliana Shaul, Michael Roth, Yungtai Lo, David S. Geller, Bang H. Hoang, Rui Yang, David Malkin, Richard Gorlick, Jonathan Gill

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P <.0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P =.0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P =.0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50.

Original languageEnglish (US)
Pages (from-to)1242-1250
Number of pages9
JournalCancer
Volume124
Issue number6
DOIs
StatePublished - Mar 15 2018

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Osteosarcoma
Pediatrics
Li-Fraumeni Syndrome
Neoplasms
Mutation
Tumor Suppressor Genes
Oncologists
Surveys and Questionnaires

Keywords

  • Li-Fraumeni syndrome
  • osteosarcoma
  • pediatrics
  • practice patterns
  • TP53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma. / Shaul, Eliana; Roth, Michael; Lo, Yungtai; Geller, David S.; Hoang, Bang H.; Yang, Rui; Malkin, David; Gorlick, Richard; Gill, Jonathan.

In: Cancer, Vol. 124, No. 6, 15.03.2018, p. 1242-1250.

Research output: Contribution to journalArticle

Shaul, Eliana ; Roth, Michael ; Lo, Yungtai ; Geller, David S. ; Hoang, Bang H. ; Yang, Rui ; Malkin, David ; Gorlick, Richard ; Gill, Jonathan. / Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma. In: Cancer. 2018 ; Vol. 124, No. 6. pp. 1242-1250.
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title = "Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma",
abstract = "BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3{\%} of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8{\%} of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7{\%} carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22{\%}) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4{\%} vs 12.4{\%}; P <.0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4{\%} vs 12.4{\%}; P =.0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4{\%} vs 10.2{\%}; P =.0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50.",
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T1 - Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma

AU - Shaul, Eliana

AU - Roth, Michael

AU - Lo, Yungtai

AU - Geller, David S.

AU - Hoang, Bang H.

AU - Yang, Rui

AU - Malkin, David

AU - Gorlick, Richard

AU - Gill, Jonathan

PY - 2018/3/15

Y1 - 2018/3/15

N2 - BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P <.0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P =.0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P =.0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50.

AB - BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P <.0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P =.0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P =.0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50.

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