A prospective interventional study evaluating seizure activity during a radiotherapy course for high-grade gliomas (SURF-ROGG)

Rades, Dirk; Witteler, Jaspar; Olbrich, Denise; Trillenberg, Peter; Schild, Steven E.; Tvilsted, Soeren; Kjær, Troels W.

doi:10.1186/s12885-021-08121-y

Cited by 6 publications

(9 citation statements)

References 20 publications

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“…However, extensive investigations have not yet been reported for GBM and therefore, seizure outcomes may differ. A prospective interventional trial evaluating the effect of RT on seizure activity in high grade (IV) gliomas is currently ongoing (Rades et al, 2021 ). Results from this study will aid understanding and inform future decisions pertaining to the application of individual anti-tumorigenic treatments in GBM patients with seizures.…”

Section: From Laboratory To Clinical Translationmentioning

confidence: 99%

Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma

Hills

Kostarelos

Wykes

2022

Front. Mol. Neurosci.

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Glioblastoma (GBM) is the most common and advanced form of primary malignant tumor occurring in the adult central nervous system, and it is frequently associated with epilepsy, a debilitating comorbidity. Seizures are observed both pre- and post-surgical resection, indicating that several pathophysiological mechanisms are shared but also prompting questions about how the process of epileptogenesis evolves throughout GBM progression. Molecular mutations commonly seen in primary GBM, i.e., in PTEN and p53, and their associated downstream effects are known to influence seizure likelihood. Similarly, various intratumoral mechanisms, such as GBM-induced blood-brain barrier breakdown and glioma-immune cell interactions within the tumor microenvironment are also cited as contributing to network hyperexcitability. Substantial alterations to peri-tumoral glutamate and chloride transporter expressions, as well as widespread dysregulation of GABAergic signaling are known to confer increased epileptogenicity and excitotoxicity. The abnormal characteristics of GBM alter neuronal network function to result in metabolically vulnerable and hyperexcitable peri-tumoral tissue, properties the tumor then exploits to favor its own growth even post-resection. It is evident that there is a complex, dynamic interplay between GBM and epilepsy that promotes the progression of both pathologies. This interaction is only more complicated by the concomitant presence of spreading depolarization (SD). The spontaneous, high-frequency nature of GBM-associated epileptiform activity and SD-associated direct current (DC) shifts require technologies capable of recording brain signals over a wide bandwidth, presenting major challenges for comprehensive electrophysiological investigations. This review will initially provide a detailed examination of the underlying mechanisms that promote network hyperexcitability in GBM. We will then discuss how an investigation of these pathologies from a network level, and utilization of novel electrophysiological tools, will yield a more-effective, clinically-relevant understanding of GBM-related epileptogenesis. Further to this, we will evaluate the clinical relevance of current preclinical research and consider how future therapeutic advancements may impact the bidirectional relationship between GBM, SDs, and seizures.

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Section: From Laboratory To Clinical Translationmentioning

confidence: 99%

Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma

Hills

Kostarelos

Wykes

2022

Front. Mol. Neurosci.

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“…The efficacy analysis will be performed on the modified Full Analysis Set defined as all patients receiving radiotherapy with a completed questionnaire at baseline and at least one completed questionnaire after start of treatment. Similar to a previous study, the statistical analyses are mainly descriptive and exploratory [ 10 ]. Sleep disorders at baseline and during radiotherapy will be rated using two patient self-reporting scales (sleep disorders and distress) and intake of sleeping drugs.…”

Section: Objectives and Endpointsmentioning

confidence: 99%

“…Similar to a previous study, patients can be identified only by an individual number and their month/year of birth [ 10 ]. Data will be handled in accordance with the General Data Protection Regulation and German regulations for radio-protection.…”

Section: Objectives and Endpointsmentioning

confidence: 99%

A prospective interventional study investigating sleep disorders prior to and during adjuvant radiotherapy for breast cancer

et al. 2021

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Background Most breast cancer patients with non-metastatic disease receive adjuvant local or loco-regional radiotherapy. To be scheduled for irradiation may cause distress and fears that can lead to sleep disorders. Few reports focused on sleep problems in patients assigned to radiotherapy. This study evaluates the course of sleep disorders during adjuvant radiotherapy for primary breast cancer and potential risk factors including the use of smartphones or tablets at bedtime. Methods The main goal is the evaluation of sleep disorders prior to radiotherapy and after 15 fractions of radiotherapy. A potential effect of habituation to the procedure of radiotherapy can be assumed that will likely lead to improvement (decrease) of sleep disorders. Improvement of sleep disorders (compared to baseline before radiotherapy) is defined as decrease of the severity of sleep disorders by ≥2 points on a patient self-rating scale (0 = no problems; 10 = maximum problems) or decrease of distress caused by sleep disorders by ≥2 points on a self-rating scale (0 = no distress; 10 = maximum distress) or reduction of the dose of sleeping drugs by ≥25%. Additional endpoints include sleep disorders after 5 fractions and at the end of radiotherapy. Moreover, potential risk factors including the use of smartphones or tablets at bedtime are evaluated. Fifty-one patients (48 plus potential drop-outs) are required. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with improvement of sleep disorders is 25% (rate under the alternative hypothesis) and assuming that a decrease of ≤10% has to be judged as a random, non-causal change in this uncontrolled study setting (null hypothesis). Discussion If a decrease of sleep disorders during the course of radiotherapy is shown, this aspect should be included in the pre-radiotherapy consent discussion with the patients. Moreover, identification of additional risk factors will likely lead to earlier psychological support. If the use of smartphones or tablets at bedtime is a risk factor, patients should be advised to change this behavior. Trial registration clinicaltrials.gov (NCT04879264; URL: https://clinicaltrials.gov/show/NCT04879264); registered on 7th of May, 2021.

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“…The study received approval by the ethics committee of the University of Lübeck, Germany (reference 20-311) and was registered at clinicaltrials.gov (identifier: NCT04552756). Eligibility criteria were previously reported and included histologically proven grade III or IV glioma, indication for normo-fractionated radiotherapy, Eastern Cooperative Oncology Group performance score of 0-2, age ≥18 years, written informed consent, and the patient's capacity to cooperate and keep the seizure diary (13).…”

mentioning

confidence: 99%

“…Radiotherapy was performed as volumetric modulated arc therapy. Further details of radiation treatment were previously described (13). Planned regimens included 59.4 Gy in 33 fractions of 1.8 Gy in 17 patients (77%) and 60 Gy in 30 fractions of 2.0 Gy in 5 patients (23%).…”

mentioning

confidence: 99%