Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study
Open accessAbstract
Background: Li‐Fraumeni Syndrome (LFS) is a rare cancer‐predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well‐characterized. Here we describe the risk of subsequent malignancy and cancer‐related death in LFS patients after undergoing RT for a first or second primary cancer. Methods: We reviewed a multi‐institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non‐RT group). Results: Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow‐up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative‐intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non‐RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy. Conclusion: We found that four of14 patients treated with RT developed in‐field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT‐induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.
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Patients with germline TP53 mutations and hereditary retinoblastoma are at particularly high risk for developing radiation-associated sarcomas.
“Patients with germline TP53 mutations as well as hereditary retinoblastoma are at particularly high risk for developing radiation-associated sarcomas and, therefore, radiation should be avoided in these individuals 123,124 .”
From Osteosarcoma (2022) · cites this paper as [124]
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- Authors
- Hendrickson, P. G., Luo, Y., Kohlmann, W., Schiffman, J., Maese, L., Bishop, A. J., Lloyd, S., Kokeny, K. E., Hitchcock, Y. J., Poppe, M. M., Gaffney, D. K., & Tao, R.
- Affiliations
- University of Utah (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Tao, Randa
- ORCID
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2020-09-15
- Volume
- 9
- Issue
- 21
- Pages
- 7954-7963
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC7643676
- OpenAlex
- W3087059636
- Cited by
- 64
- References
- 31
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 14 · 2023: 8 · 2022: 11 · 2021: 7
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- University of Utah (P30 CA042014)
- Huntsman Cancer Institute (P30CA042014)
- National Institutes of Health (5ul1tr001067-05)
- National Cancer Institute (P30CA042014)
- National Center for Advancing Translational Sciences (UL1-TR001067)
- Topics
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- Li-Fraumeni syndrome, radiotherapy, secondary malignancies, germline TP53 mutation, hereditary cancer predisposition, cancer-related death, in-field recurrence, radiation-induced cancer, curative-intent radiotherapy
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasms, Radiation-Induced, Radiotherapy, Registries, Retrospective Studies, Risk Factors, Time Factors, United States, Tumor Suppressor Protein p53, Neoplasms, Second Primary, Li-Fraumeni Syndrome, Treatment Outcome, Germ-Line Mutation, Risk Assessment, Genetic Predisposition to Disease, Young Adult
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