Radiation-Induced Cerebral Microbleeds in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy

Kralik, Stephen F.; Mereniuk, Todd R.; Grignon, L; Shih, Chie Schin; Ho, Chang Yueh; Finke, Whitney; Coleman, Peter W.; Watson, Gordon A.; Buchsbaum, Jeffrey C.

doi:10.1016/j.ijrobp.2018.07.2016

Cited by 27 publications

(25 citation statements)

References 30 publications

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“…Although it has been taught that proton beam radiotherapy could be less harmful than photon radiotherapy because the radiation does not scatter to surrounding tissues, recent studies have shown large-vessel vasculopathy and high incidence of microbleeds after proton beam radiotherapy. 18 , 40 However, we did not find a lower rate of CVD in those treated with local radiotherapy, which may be related to fewer glial cell tumors, and thus less local radiotherapy in the survivors with shorter follow-up time. However, even stereotactic radiotherapy reduces cerebral blood flow in the surrounding tissue, which suggests that irradiation may harm the brain vasculature beyond the radiation field.…”

Section: Discussioncontrasting

confidence: 60%

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Remes

Suo‐Palosaari

Koskenkorva

et al. 2020

Neuro-Oncology Practice

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Abstract Background Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files. Results Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

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Section: Discussioncontrasting

confidence: 60%

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Remes

Suo‐Palosaari

Koskenkorva

et al. 2020

Neuro-Oncology Practice

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“…32,33 Prior studies of pediatric patients treated with PBT for intracranial tumors have demonstrated the association of both subclinical and clinical vasculopathy with increased RT dose. 34,35 This therefore may account for the observation in this series of higher PsP rates among patients treated with higher RT doses. With regard to RT modality, it is noteworthy that 96% of PBT-treated patients received passive scattering PBT.…”

Section: Discussionmentioning

confidence: 72%

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy

et al. 2019

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Background. Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT). Methods. Serial MRI scans from 83 pediatric LGG patients managed at 2 institutions between 1998 and 2017 were evaluated. PsP was scored when a progressive lesion subsequently decreased or stabilized for at least a year without therapy. Results. Thirty-two patients (39%) were treated with IMRT, and 51 (61%) were treated with PBT. Median RT dose for the cohort was 50.4 Gy(RBE) (range, 45-59.4 Gy[RBE]). PsP was identified in 31 patients (37%), including 8/32 IMRT patients (25%) and 23/51 PBT patients (45%). PBT patients were significantly more likely to have post-RT enlargement (hazard ratio [HR] 2.15, 95% CI: 1.06-4.38, P = 0.048). RT dose >50.4 Gy(RBE) similarly predicted higher rates of PsP (HR 2.61, 95% CI: 1.20-5.68, P = 0.016). Multivariable analysis confirmed the independent effects of RT modality (P = 0.03) and RT dose (P = 0.01) on PsP incidence. Local progression occurred in 10 patients: 7 IMRT patients (22%) and 3 PBT patients (6%), with a trend toward improved local control for PBT patients (HR 0.34, 95% CI: 0.10-1.18, P = 0.099). Conclusions. These data highlight substantial rates of PsP among pediatric LGG patients, particularly those treated with PBT. PsP should be considered when assessing response to RT in LGG patients within the first year after RT. AQ2 Key Points 1. Pseudoprogression is common following radiotherapy (RT) among pediatric patients with low-grade glioma. 2. Pseudoprogression rates were higher among those treated with proton RT (compared with photon RT), and among those treated with higher doses of RT. 3. Local control is excellent among pediatric low-grade glioma patients treated with RT, irrespective of RT modality. Pediatric low-grade glioma (LGG), comprising World Health Organization (WHO) grades I and II primary glial neoplasms, can be treated using a variety of therapeutic strategies, including surgery, systemic therapy, and radiotherapy (RT). 1,2 Due to concerns regarding long-term sequelae, RT is generally included in the treatment of pediatric LGG 687 Ludmir et al. Pseudoprogression risk for pediatric LGG patients Neuro-Oncology

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“…Currently, there is not enough data on possible differences between CMBs occurrence after photon vs proton therapy. Based on two available studies, the pattern of CMBs occurrence on MRI seems to be similar for photon and proton radiation therapy for both whole brain radiotherapy (WBRT) and focal radiation fields [50,58]. The first CMBs appeared already 3 months after proton therapy onset, with an increasing prevalence over time, especially within the first few years.…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

“…The first CMBs appeared already 3 months after proton therapy onset, with an increasing prevalence over time, especially within the first few years. Furthermore, the number of CMBs was related to risk factors, such as younger age and higher maximum radiation therapy dose [58]. In the case of proton therapy the highest amount of CMBs was found within the dose fields over 30 Gy [58].…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

Quantifying effects of radiotherapy-induced microvascular injury; review of established and emerging brain MRI techniques

Laar

Sinnige

et al. 2019

Radiotherapy and Oncology

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Radiation-Induced Cerebral Microbleeds in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy

Cited by 27 publications

References 30 publications

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy

Quantifying effects of radiotherapy-induced microvascular injury; review of established and emerging brain MRI techniques

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