Subsequent Malignancies in Patients With Li-Fraumeni Syndrome Treated With Radiation Therapy

Suri, J.S.; Rednam, Surya P.; Teh, Bin S.; Butler, Eboneé N.; Paulino, Arnold C.

doi:10.1016/j.ijrobp.2013.06.186

Cited by 9 publications

(7 citation statements)

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“…This same limitation applies to a review by Suri et al which reported a cumulative incidence of secondary malignancy after RT as high as 48% (which is similar to our subsequent malignancy rate prior to further classification) in 11 out of a total of 23 pooled patients from 10 articles and case reports; however, they did not define what constituted a secondary malignancy. 21 Despite the limitations in these studies, it is important to note that the numbers are consistent with a smaller cohort studies such as one by Heymann et al that reported specifically on the incidence of radiation-induced cancers in LFS patients treated for primary breast cancer. 22 In that study, two of six (33%) LFS patients developed new primary tumors in the radiation field, both of which were temporally and histologically compatible with radiation-induced malignancies.…”

Section: Discussionsupporting

confidence: 71%

“…Though alarming, it is unclear from this study what fraction of these cancers represent true radiation‐associated secondary malignancies versus recurrent or progressive disease. This same limitation applies to a review by Suri et al which reported a cumulative incidence of secondary malignancy after RT as high as 48% (which is similar to our subsequent malignancy rate prior to further classification) in 11 out of a total of 23 pooled patients from 10 articles and case reports; however, they did not define what constituted a secondary malignancy 21 . Despite the limitations in these studies, it is important to note that the numbers are consistent with a smaller cohort studies such as one by Heymann et al that reported specifically on the incidence of radiation‐induced cancers in LFS patients treated for primary breast cancer 22 .…”

Section: Discussionmentioning

confidence: 60%

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Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study

et al. 2020

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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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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 60%

Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study

et al. 2020

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“…This way, based on pre-trained data sets, there would be a possibility to detect an individual hypersensitivity to irradiation via organoid DDR kinetics. This approach would be particularly significant in the patient cases bearing an innate DDR alternations, such as Fanconi anemia [47] and Li-Fraumeni syndrome [48], which are prone to secondary cancer formation.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Normal Tissue Radiosensitivity by Evaluating DNA Damage and Repair Kinetics in Human Brain Organoids

Bojcevski

Wang

Liu

et al. 2021

IJMS

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DNA-double strand break (DSB), detected by immunostaining of key proteins orchestrating repair, like γH2AX and 53BP1, is well established as a surrogate for tissue radiosensitivity. We hypothesized that the generation of normal brain 3D organoids (“mini-brains”) from human induced pluripotent stem cells (hiPSC) combined with detection of DNA damage repair (DDR) may hold the promise towards developing personalized models for the determination of normal tissue radiosensitivity. In this study, cerebral organoids, an in vitro model that stands in its complexity between 2D cellular system and an organ, have been used. To quantify radiation-induced response, immunofluorescent staining with γH2AX and 53BP1 were applied at early (30 min, initial damage), and late time points (18 and 72 h, residual damage), following clinical standard 2 Gy irradiation. Based on our findings, assessment of DDR kinetics as a surrogate for radiosensitivity in hiPSC derived cerebral organoids is feasible. Further development of mini-brains recapitulating mature adult neuronal tissue and implementation of additional signaling and toxicity surrogates may pave the way towards development of next-generation personalized assessment of radiosensitivity in healthy neuronal tissue.

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“…The total world literature on using radiation therapy in patients with Li-Fraumeni is limited, but as much as a 70% risk of secondary cancer after radiation therapy has been reported in 1 review. 47 Heymann et al reported that among 6 patients with Li-Fraumeni syndrome who received adjuvant radiation therapy, 11 events occurred, 2 of which were definitely attributed to radiation treatment. There may also be allelespecific effects that modulate the risks.…”

Section: Genetic Syndromes Associated With Increased Risk Of Radiatiomentioning

confidence: 99%

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

Bergom

West

Higginson

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxiatelangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

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Subsequent Malignancies in Patients With Li-Fraumeni Syndrome Treated With Radiation Therapy

Cited by 9 publications

References 0 publications

Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study

Radiation therapy and secondary malignancy in Li‐Fraumeni syndrome: A hereditary cancer registry study

Assessment of Normal Tissue Radiosensitivity by Evaluating DNA Damage and Repair Kinetics in Human Brain Organoids

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

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