Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study.
Adolescent
Adult
Child
Child, Preschool
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Infant
Infant, Newborn
Li-Fraumeni Syndrome
/ diagnosis
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasms, Radiation-Induced
/ etiology
Neoplasms, Second Primary
Radiotherapy
/ adverse effects
Registries
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Tumor Suppressor Protein p53
/ genetics
United States
Young Adult
LFS
Li-Fraumeni syndrome
RT-induced malignancy
p53
radiation
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
29
07
2020
accepted:
31
07
2020
pubmed:
16
9
2020
medline:
20
7
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32931654
doi: 10.1002/cam4.3427
pmc: PMC7643676
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7954-7963Subventions
Organisme : NCI NIH HHS
ID : P30 CA042014
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001067
Pays : United States
Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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