International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationCerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries
Introduction
It is well established that exposure to radiation increases the risk of stroke, and the dose response to radiation has been investigated in several studies (1). Nevertheless, present knowledge is insufficient to predict the long-term risk of stroke after radiation therapy (RT) because the dose response to fractionated high doses of radiation to the brain is not known. This lack of knowledge is of special concern for RT to children because of the greater radiation sensitivity of children. Although the spinal cord, optic nerves, and chiasma are considered organs at risk (OARs) under national guidelines for RT, the cerebral arteries are not 2, 3.
Mortality due to cerebrovascular diseases has been studied in large cohorts of childhood cancer survivors 4, 5, 6, and stroke risk has been studied in long-term survivors of Hodgkin disease (7), leukemia, and brain tumors (8).
The role of the maximal radiation dose received during cranial irradiation in the risk of stroke (9) and in the risk of recurrent stroke in survivors who have experienced a first stroke (10) has been investigated in the large United States Childhood Cancer Survival Study (CCSS). Nevertheless, the same maximal radiation dose received during cranial irradiation could recover very different dose distributions and therefore very different radiation doses to the OARs to be considered when the relation between irradiation and stroke risk is investigated. Additionally, new RT modalities and treatment techniques, which include intensity modulated RT (IMRT) and proton therapies, result in different organ dose distributions.
To be able to anticipate the stroke risk in former patients, and to predict the stroke risk of current treatments, it is necessary to identify such OARs and to investigate the role of radiation dose received by these organs and its potential dose-response modifiers in the risk of stroke. The aim of this study was to evaluate these risk factors in a cohort of 3172 5-year survivors of solid childhood cancer.
Section snippets
Patients
Euro2K is a retrospective cohort of children treated from 1942 to 1985 in 8 centers in France and the United Kingdom. It was constituted from 1985 to 1995, and the children have been prospectively followed up since. To be included in the cohort, the patients had to be alive 2 years (France) or 3 years (UK) after a first cancer diagnosis before the age of 16 years (before 15 in UK centers). The constitution of the cohort was first described in 1995 (11). In this publication, the cohort included
Radiation dose pattern: Circle of Willis
The average radiation dose received to the WC arteries was 22 Gy for brain tumors, 13 Gy for non-Hodgkin lymphoma (NHL), and 9 Gy for retinoblastoma (Fig. E2; available online at www.redjournal.org). The high radiation dose to the WC (13 Gy) for the NHL is due to the fact that prophylactic irradiation of the brain was quasisystematic in France for NHL before 1974 and for high-grade NHL afterward.
Stroke risk
During a median follow-up time of 26 years, 54 patients experienced a permanent stroke that could be
Discussion
To our knowledge, this is the first study to investigate in detail the relation between the radiation dose to the WC arteries, rather than the maximal radiation dose received to the brain, and the risk of late-occurring strokes after childhood cancer. It included medical validation and a complete description of the type and location of each stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median of 26 years. It indicated that the main risk factor for
Acknowledgment
The authors thank Martine Labbé, MSc, and Catherine Paoletti, MSc for their help in data management, and the physicians and physicists who participated in the elaboration of the study or data collection at the Gustave Roussy (Villejuif), Thames Cancer Registry (London), Institut Godinot (Reims), Institut Curie (Paris), Centre Regaud (Toulouse), and Centre Lacassagne (Nice).
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2022, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Although technically different, cumulative incidence of stroke by an attained age of 45 and the prevalence of stroke in an individual at the age of 45 should yield similar rates. We used values that were previously published by El-Fayech10 for their study population, suggesting a baseline cumulative incidence of stroke of 0.22% at an attained age of 35 years and 0.52% at an attained age of 45 years in the general population. The incidence of stroke was very similar in the general population and pediatric cancer survivors who received either no RT or <1 Gy, until the age of 45.
Imaging of Neurologic Injury following Oncologic Therapy
2021, Radiologic Clinics of North AmericaChildhood cancer: Survival, treatment modalities, late effects and improvements over time
2021, Cancer EpidemiologyCitation Excerpt :Three large studies with unique data deriving from the EU-funded PanCareSurFup consortium (www.pancaresurfup.eu) demonstrated a 22- and a 30-fold increased risk of subsequent primary bone cancer and soft-tissue sarcomas in five-year childhood cancer survivors, respectively [75,77], and a four-fold increased risk of subsequent leukaemias [76] compared to population norms. Other studies have often focused on a single health outcome or organ system [79–89] (Table 3). Compared to the general population or siblings, some of these studies reported a 4.8-fold increased risk of hospital contact for any endocrine disorder [82], an 8.5-fold increased risk of stroke among irradiated survivors [81], a 6.8-fold increased risk of respiratory mortality [86], and more frequent hearing loss among survivors of childhood cancer [87].
Ionizing radiation-induced circulatory and metabolic diseases
2021, Environment InternationalCitation Excerpt :Recent studies have suggested radiation-associated excess morbidity and mortality in groups of childhood cancer survivors (Table S1) (El-Fayech et al., 2017; Haddy et al., 2016; Mulrooney et al., 2009; Tukenova et al., 2010a). The RT organ dosimetry is of variable quality, but higher in the French childhood cancer cohort (El-Fayech et al., 2017; Haddy et al., 2016; Tukenova et al., 2010b), in that it is fully individualized, based on Monte Carlo reconstructions derived from individual treatment records (Diallo et al., 1996; Shamsaldin et al., 1998). The US study adjusted for tobacco use (Mulrooney et al., 2009), and although data on smoking and body mass index was available in some studies (El-Fayech et al., 2017; Haddy et al., 2016), adjustment for these did not materially alter results.
Supported by the Ligue Nationale Contre le Cancer, CerebRad FP7 project (Grant Agreement No. 295552), Institut de Recherche en Santé Publique, Programme Hospitalier de Recherche Clinique, Electricité de France, the Fondation Force, the Wyeth Foundation for Childhood and Adolescent Health, National Institute of Cancer, and the Agence Nationale Pour la Recherche.
Conflict of interest: none.