Radiation-Induced Malignancies Making Radiotherapy a “Two-Edged Sword”: A Review of Literature

Singh, Gunjesh Kumar; Yadav, Vikas; Singh, Pragya; Bhowmik, K.T.

doi:10.14740/wjon996w

Cited by 45 publications

(43 citation statements)

References 45 publications

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“…We compared the patient’s clinical history with the criteria defined by Cahan et al [ 31 ], which is currently being used as the standard to define radiation-induced malignancies [ 32 ]. The patient had no genetic predisposition for the development of secondary tumours, and the brainstem tumour arose within the irradiated field, occurred more than four years after the delivery of radiation, and was histologically distinct from the primary medulloblastoma, thereby satisfying all criteria to be considered a radiation-induced secondary tumour.…”

Section: Resultsmentioning

confidence: 99%

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

Whitehouse

Howlett

Hii

et al. 2020

Cancers

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Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phosphorylated S6, 4EBP1 and ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.

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Section: Resultsmentioning

confidence: 99%

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

Whitehouse

Howlett

Hii

et al. 2020

Cancers

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“…Time to follow‐up, time to subsequent malignancy, and time to death measurements were calculated from the date of the first cancer diagnosis. The modified Cahan's criteria described by Singh et al were considered to determine whether or not a “subsequent malignancy” was radiation induced 16 . Briefly, subsequent cancers needed to be of a different histology and must have occurred in a previously irradiated field after a sufficient latency period.…”

Section: Methodsmentioning

confidence: 99%

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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“…Jedním z nejzávažnějších důsledků radiační expozice je radiačně indukovaná malignita (RIM). Ačkoli patogeneze není dobře definována, možným mechanizmem může být mutace normálních tkání radiačně indukovaným poškozením, zvláště u dětských pacientů [4].…”

Section: úVodunclassified

“…: leukemie vznikají v orgánech, které obdržely záření o nízké dávce a považují se také za sekundární nádory); 2) musí existovat dostatečná doba latence mezi ozařováním a vznikem dalšího nádoru, nejlépe > 4 roky; 3) histologicky se jedná o jiný druh nádoru (nutné histologické ověření); 4) tkáň, ve které vznikl údajný indukovaný nádor, musí být před expozicí záření normální (tj. metabolicky a geneticky) [4,5].…”

Section: Cahanova Kritériaunclassified

Secondary tumors and radiotherapy

Šlampa¹,

Šlampa²

2020

Klin Onkol

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Východiska: Radioterapie se považuje za potencionální karcinogenní faktor, nicméně pacient s vyléčeným nádorem má min. 14% riziko vzniku dalšího nádoru bez ohledu na předcházející protinádorovou systémovou terapii nebo radioterapii. Na zvýšeném riziku vzniku sekundárních zhoubných nádorů mají svůj podíl protinádorová systémová léčba, radioterapie a samozřejmě i genetické predispozice; to je nepochybné. I nižší věk nemocného má vliv na zvýšení rizika vzniku radiačně indukovaných nádorů. S moderní účinnou protinádorovou léčbou lze předpokládat další prodloužení přežívání nemocných s malignitami, a tedy vyšší výskyt sekundárních nádorů. Empiricky lze konstatovat, že řada publikovaných prací, které popisují vznik sekundárních nádorů po léčbě zářením, nevychází z definice sekundárního nádoru podle Cahanových kritérií (především: sekundární nádor se musí vyskytovat v ozařovaném poli, histologicky se jedná o jiný druh nádoru a minimální doba latence má být delší než 4 roky). Cíl: V práci je uveden přehled retrospektivních studií na téma sekundárních nádorů, dále přehled častých sekundárních malignit, jejich možná příčina se zaměřením na radioterapii a možnosti snížení rizika radiačně indukovaných malignit za použití moderních technik radioterapie, použití nižších energií a redukce ozařovaných objemů. Závěr: Riziko radiačně indukovaných nádorů je často v reklamě a na sociálních sítích z komerčních důvodů zbytečně nadhodnoceno. Klíčová slova radioterapie-sekundární nádory-radiačně indukované nádory Summary Background: Radiotherapy is considered a potential carcinogenic factor; however, a patient with a cured tumor has a min. 14% risk of developing another tumor regardless of previous anticancer systemic therapy or radiotherapy. However, anticancer systemic therapy, radiotherapy, and, of course, genetic predispositions, contribute to the increased risk of developing secondary cancers; that is undoubted. Even the younger age of the patient has an effect on the increased risk of radiation-induced malignancies. With modern effective anticancer treatment, a further prolongation of the survival of patients with malignancies, and thus a higher incidence of secondary tumors, can be expected. Empirically, it can be stated that many published works that describe the formation of secondary tumors after radiation treatment are not based on the definition of a secondary tumor according to the Cahan criteria (especially: the secondary tumor must occur in the irradiated field, histologically it is a different type of tumor and the minimum latency should be longer than 4 years). Purpose: The article presents an overview of retrospective studies on the topic of secondary tumors, an overview of common secondary malignancies, their possible cause with a focus on radiotherapy and the possibility of reducing the risk of radiation-induced malignancies using modern radiotherapy techniques, lower energies and reduced radiation volumes. Conclusion: The risk of radiation-induced tumors is often unnecessarily overestimated in advertising and on soc...

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Radiation-Induced Malignancies Making Radiotherapy a “Two-Edged Sword”: A Review of Literature

Cited by 45 publications

References 45 publications

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

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

Secondary tumors and radiotherapy

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