Radiation and Brain Tumors: An Overview

Grunert, Michael; Kassubek, Rebecca; Danz, B.; Klemenz, Burkhard; Hasslacher, Sebastian; Stroh, Sebastien; Schneele, Lukas; Barry, Sara E; Zhou, Shaoxia; Debatin, Klaus‐Michael; Westhoff, Mike‐Andrew

doi:10.1615/critrevoncog.2018025927

Cited by 24 publications

(12 citation statements)

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“…While there can be little doubt about the importance of radiation as part of the standard cancer therapy, there are still unwanted consequences of applying it, such as increase motility in the surviving fraction of tumour cells ( 63 ). For example, following 10 Gy irradiation, surviving lung cancer cells exhibit both an increased motility and invasiveness ( 39 ), via molecular pathways we have also observed to be increased in stressed glioblastoma cells ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells

Hasslacher¹,

Schneele²,

Stroh³

et al. 2018

Int J Oncol

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Glioblastoma, the most common primary brain tumour, is also considered one of the most lethal cancers per se. It is highly refractory to therapeutic intervention, as highlighted by the mean patient survival of only 15 months, despite an aggressive treatment approach, consisting of maximal safe surgical resection, followed by radio- and chemotherapy. Radiotherapy, in particular, can have effects on the surviving fractions of tumour cells, which are considered adverse to the desired clinical outcome: It can induce increased cellular proliferation, as well as enhanced invasion. In this study, we established that differentiated glioblastoma cells alter their DNA repair response following repeated exposure to radiation and, therefore, high single-dose irradiation (SD-IR) is not a good surrogate marker for fractionated dose irradiation (FD-IR), as used in clinical practice. Integrating irradiation into a combination therapy approach, we then investigated whether the pharmacological inhibition of PI3K signalling, the most abundantly activated survival cascade in glioblastoma, enhances the efficacy of radiotherapy. Of note, treatment with GDC-0941, which blocks PI3K-mediated signalling, did not enhance cell death upon irradiation, but both treatment modalities functioned synergistically to reduce the total cell number. Furthermore, GDC-0941 not only prevented the radiation-induced increase in the motility of the differentiated cells, but further reduced their speed below that of untreated cells. Therefore, combining radiotherapy with the pharmacological inhibition of PI3K signalling is a potentially promising approach for the treatment of glioblastoma, as it can reduce the unwanted effects on the surviving fraction of tumour cells.

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Section: Discussionmentioning

confidence: 99%

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells

Hasslacher¹,

Schneele²,

Stroh³

et al. 2018

Int J Oncol

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“…It has been demonstrated to increase patient survival rates and improve quality of life. 1,2 The conventional treatment technique for both identifiable brain metastasis and prophylaxis for microscopic disease is stereotactic radiosurgery (SRS)/stereotactic radiation therapy (SRT) with or without whole brain radiation therapy. 3 SRS provides accurate delivery of a high dose of radiation to a target in a single fraction while sparing the surrounding normal tissue.…”

Section: Introductionmentioning

confidence: 99%

Dose Gradient Index for Stereotactic Radiosurgery/Radiation Therapy

Reynolds

Jensen

Bellairs

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Purpose: Steep dose falloff outside of tumors is a hallmark of stereotactic radiosurgery (SRS) and radiation therapy (SRT). Dose gradient index (DGI) quantifies the dose drop off. Tables of DGIs versus target volumes have been published for body sites, but none is available for brain. This study recommends guidelines for DGIs for brain SRS/SRT treatments based on clinical CyberKnife (CK) cases. Methods and Materials: Four hundred ninety-five plans for patients with central nervous system tumors treated with CK at our institution between March 2015 and May 2018 were analyzed. The CK treatment planning system MultiPlan was used for planning. SRS/SRT plans were stratified into 6 groups by tumor size (Group I [0-1 cm 3 ], II [1.0-3.0 cm 3 ], III [3.0-5.0 cm 3 ], IV [5.0-10.0 cm 3 ], V [10.0-15.0 cm 3 ], and VI [15.0-40.0 cm 3 ]). Ideal and minimally acceptable DGIs were determined for each size group. To evaluate the effect of target shape on DGI criteria, the plans were divided into 4 target shape groups: (1) homogeneous shape (circular), (2) adjacent to radiosensitive organs at risk (adjacent), (3) irregularly shaped (irregular), and (4) multiple target plans (multilesion). The mean for each target size group was defined as the ideal DGI. Minimally acceptable DGI criteria are specified to reject the lowest 10% of cases. Results: The minimal acceptable DGIs were 83 (Group I), 72 (II), 65 (III), 58 (IV), 52 (V), and 35 (VI). The ideal DGI is designated to evaluate SRS/SRT plans for homogeneous circular lesions, whereas minimal DGI is chosen to assess the plans for irregular, adjacent to organs at risk, and multilesions. SRS/SRT plans with higher DGI values are correlated with lower irradiated normal tissue volumes. Conclusions: This study provides a table of DGIs for brain SRS/SRT treatments as a tool for assessing the quality of intracranial SRS/SRT plans. DGI guidelines support SRS/SRT planning that results in lower risk of radionecrosis. Ó

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“…Radiation causes damages directly on DNA strands and on RNA and destroying all the cellular bilayers, by inducing calcium inflow, stimulating apoptosis by mechanisms not completely understood [14,15]. Preclinical molecular studies have clarified that radio-induced brain damage is correlated with radiation exposure, the total administered dose, dose per fraction, and the duration of irradiation [16].…”

Section: Introductionmentioning

confidence: 99%

An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy

Moretti

Caruso

2020

IJMS

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We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.

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Radiation and Brain Tumors: An Overview

Cited by 24 publications

References 0 publications

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells

Dose Gradient Index for Stereotactic Radiosurgery/Radiation Therapy

An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy

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