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Strahlentherapie Und Onkologie : Organ... Nov 2022The Working Group for Neurooncology of the German Society for Radiation Oncology (DEGRO; AG NRO) in cooperation with members of the Neurooncological Working Group of the... (Review)
Review
PURPOSE
The Working Group for Neurooncology of the German Society for Radiation Oncology (DEGRO; AG NRO) in cooperation with members of the Neurooncological Working Group of the German Cancer Society (DKG-NOA) aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS).
METHODS
Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN, including bevacizumab, in clinical routine.
CONCLUSION
Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neurooncologist. If the diagnosis of blood-brain barrier disruptions (BBD) or RN is likely, treatment should be initiated depending on the symptoms, location, and dynamic of the lesion. Multiple treatment options are available (such as observation, surgery, steroids, and bevacizumab) and the optimal approach should be discussed in an interdisciplinary setting. In this practice guideline, we offer detailed treatment strategies for various scenarios.
Topics: Humans; Radiosurgery; Bevacizumab; Radiation Injuries; Central Nervous System; Necrosis
PubMed: 36038670
DOI: 10.1007/s00066-022-01973-8 -
Langmuir : the ACS Journal of Surfaces... Mar 2023Cell responses to external radiofrequencies (RF) are a fundamental problem of much scientific research, clinical applications, and even daily lives surrounded by...
Cell responses to external radiofrequencies (RF) are a fundamental problem of much scientific research, clinical applications, and even daily lives surrounded by wireless communication hardware. In this work, we report an unexpected observation that the cell membrane can oscillate at the nanometer scale in phase with the external RF radiation from kHz to GHz. By analyzing the oscillation modes, we reveal the mechanism behind the membrane oscillation resonance, membrane blebbing, the resulting cell death, and the selectivity of plasma-based cancer treatment based on the difference in the membrane's natural frequencies among cell lines. Therefore, a selectivity of treatment can be achieved by aiming at the natural frequency of the target cell line to focus the membrane damage on the cancer cells and avoid normal tissues nearby. This gives a promising cancer therapy that is especially effective in the mixing lesion of the cancer cells and normal cells such as glioblastoma where surgical removal is not applicable. Along with these new phenomena, this work provides a general understanding of the cell coupling with RF radiation from the externally stimulated membrane behavior to the cell apoptosis and necrosis.
Topics: Radio Waves; Cell Membrane; Cell Line; Electromagnetic Fields
PubMed: 36802616
DOI: 10.1021/acs.langmuir.2c03181 -
Journal of Neuropathology and... Jul 2020Cerebral radiation necrosis (CRN) is a delayed complication of radiosurgery that can result in severe neurological deficits. The biological changes leading to necrotic...
Cerebral radiation necrosis (CRN) is a delayed complication of radiosurgery that can result in severe neurological deficits. The biological changes leading to necrotic damage may identify therapeutic targets for this complication. Connexin43 expression associated with chronic inflammation may presage the development of CRN. A mouse model of delayed CRN was used. The left hemispheres of adult female mice were irradiated with single-fraction, high-dose radiation using a Leksell Gamma Knife. The brains were collected 1 and 4 days, and 1-3 weeks after the radiation. The expression of connexin43, interleukin-1β (IL-1β), GFAP, isolectin B-4, and fibrinogen was evaluated using immunohistochemical staining and image analysis. Compared with the baseline, the area of connexin43 and IL-1β staining was increased in ipsilateral hemispheres 4 days after radiation. Over the following 3 weeks, the density of connexin43 gradually increased in parallel with progressive increases in GFAP, isolectin B-4, and fibrinogen labeling. The overexpression of connexin43 in parallel with IL-1β spread into the affected brain regions first. Further intensified upregulation of connexin43 was associated with escalated astrocytosis, microgliosis, and blood-brain barrier breach. Connexin43-mediated inflammation may underlie radiation necrosis and further investigation of connexin43 hemichannel blockage is merited for the treatment of CRN.
Topics: Animals; Brain; Brain Injuries; Connexin 43; Female; Gene Expression; Inflammation; Mice; Mice, Inbred BALB C; Necrosis; Radiation Injuries
PubMed: 32447392
DOI: 10.1093/jnen/nlaa037 -
International Journal of Hyperthermia :... Jul 2020Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with... (Review)
Review
Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with arteriovenous malformations and brain metastases but possibly also affecting patients treated with radiosurgery for meningioma. The pathophysiology of radiation necrosis is still not well understood but is most likely a secondary local tissue inflammatory response to brain tissue injured by radiation. Radiation necrosis in brain metastases patients may present radiographically and behave clinically like recurrent tumor. Differentiation between radiation necrosis and recurrent tumor has been difficult based on radiographic changes alone. Biopsy or craniotomy therefore remains the gold standard method of diagnosis. For symptomatic patients, corticosteroids are first-line therapy, but patients may fail medical management due to intolerance of chronic steroids or persistence of symptoms. In these cases, open surgical resection has been shown to be successful in management of surgically amenable lesions but may be suboptimal in patients with deep-seated lesions or extensive prior cranial surgical history, both carrying high risk for peri-operative morbidity. Laser interstitial thermal therapy has emerged as a viable, alternative surgical option. In addition to allowing access to tissue for diagnosis, thermal treatment of the lesion can also be delivered precisely and accurately under real-time imaging guidance. This review highlights the pertinent studies that have shaped the impetus for use of laser interstitial thermal therapy in the treatment of radiation necrosis, reviewing indications, outcomes, and nuances toward successful application of this technology in patients with suspected radiation necrosis.
Topics: Brain Neoplasms; Humans; Hyperthermia, Induced; Laser Therapy; Lasers; Necrosis; Neoplasm Recurrence, Local; Radiation Injuries; Radiosurgery
PubMed: 32672119
DOI: 10.1080/02656736.2020.1760362 -
International Review of Neurobiology 2020Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the... (Review)
Review
Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progression (PD) and radiation necrosis (RN) remains a challenge. Therefore, accurate and reliable imaging evaluation is very important for making clinical decisions. In recent years, advanced multimodal imaging techniques have been applied to achieve the goal of better differentiating glioma recurrence from post-radiotherapy changes for minimizing errors associated with interpretation of treatment effects. In this review, we discuss the recent applications of advanced multimodal imaging such as diffusion MRI sequences, amide proton transfer MRI sequences, perfusion MRI sequences, MR spectroscopy and multinuclides PET/CT in the evaluation of post-radiotherapy treatment response in glioma patients and highlight their potential role in differentiating post-radiotherapy changes from glioma recurrence.
Topics: Brain Neoplasms; Disease Progression; Glioma; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Necrosis; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Radiation Injuries
PubMed: 32448612
DOI: 10.1016/bs.irn.2020.03.009 -
Molecular Imaging and Biology Jun 2021Differentiation between radiation-induced necrosis and tumor recurrence is crucial to determine proper management strategies but continues to be one of the central...
PURPOSE
Differentiation between radiation-induced necrosis and tumor recurrence is crucial to determine proper management strategies but continues to be one of the central challenges in neuro-oncology. We hypothesized that hyperpolarized C MRI, a unique technique to measure real-time in vivo metabolism, would distinguish radiation necrosis from tumor on the basis of cell-intrinsic metabolic differences. The purpose of this study was to explore the feasibility of using hyperpolarized [1-C]pyruvate for differentiating radiation necrosis from brain tumors.
PROCEDURES
Radiation necrosis was initiated by employing a CT-guided 80-Gy single-dose irradiation of a half cerebrum in mice (n = 7). Intracerebral tumor was modeled with two orthotopic mouse models: GL261 glioma (n = 6) and Lewis lung carcinoma (LLC) metastasis (n = 7). C 3D MR spectroscopic imaging data were acquired following hyperpolarized [1-C]pyruvate injection approximately 89 and 14 days after treatment for irradiated and tumor-bearing mice, respectively. The ratio of lactate to pyruvate (Lac/Pyr), normalized lactate, and pyruvate in contrast-enhancing lesion was compared between the radiation-induced necrosis and brain tumors. Histopathological analysis was performed from resected brains.
RESULTS
Conventional MRI exhibited typical radiographic features of radiation necrosis and brain tumor with large areas of contrast enhancement and T2 hyperintensity in all animals. Normalized lactate in radiation necrosis (0.10) was significantly lower than that in glioma (0.26, P = .004) and LLC metastatic tissue (0.25, P = .00007). Similarly, Lac/Pyr in radiation necrosis (0.18) was significantly lower than that in glioma (0.55, P = .00008) and LLC metastasis (0.46, P = .000008). These results were consistent with histological findings where tumor-bearing brains were highly cellular, while irradiated brains exhibited pathological markers consistent with reparative changes from radiation necrosis.
CONCLUSION
Hyperpolarized C MR metabolic imaging of pyruvate is a noninvasive imaging method that differentiates between radiation necrosis and brain tumors, providing a groundwork for further clinical investigation and translation for the improved management of patients with brain tumors.
Topics: Animals; Brain; Brain Neoplasms; Carbon Isotopes; Cell Line, Tumor; Disease Models, Animal; Magnetic Resonance Imaging; Mice; Necrosis; Neoplasm Transplantation; Radiation Injuries
PubMed: 33442835
DOI: 10.1007/s11307-020-01574-w -
Neurosurgical Focus Aug 2023Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of...
OBJECTIVE
Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM.
METHODS
The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses.
RESULTS
The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans.
CONCLUSIONS
Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.
Topics: Humans; Middle Aged; Adolescent; Carcinoma, Non-Small-Cell Lung; Radiosurgery; Retrospective Studies; Lung Neoplasms; Treatment Outcome; Brain Neoplasms; Necrosis
PubMed: 37527673
DOI: 10.3171/2023.5.FOCUS23209 -
Journal of Neuro-oncology Aug 2023We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without...
Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.
PURPOSE
We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO).
METHODS
From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method.
RESULTS
Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1).
CONCLUSION
The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.
Topics: Humans; Brain Neoplasms; Hemorrhage; Melanoma; Necrosis; Radiation Injuries; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 37552363
DOI: 10.1007/s11060-023-04404-5 -
International Journal of Radiation... Sep 2019Near-infrared (NIR) and red-to-near-infrared (R/NIR) radiation are increasingly applied for therapeutic use. R/NIR-employing therapies aim to stimulate healing, prevent... (Review)
Review
Near-infrared (NIR) and red-to-near-infrared (R/NIR) radiation are increasingly applied for therapeutic use. R/NIR-employing therapies aim to stimulate healing, prevent tissue necrosis, increase mitochondrial function, and improve blood flow and tissue oxygenation. The wide range of applications of this radiation raises questions concerning the effects of R/NIR on the immune system. In this review, we discuss the potential effects of exposure to R/NIR light on immune cells in the context of physical parameters of light. The effects that R/NIR may induce in immune cells typically involve the production of reactive oxygen species (ROS), nitrogen oxide (NO), or interleukins. Production of ROS after exposure to R/NIR can either be inhibited or to some extent increased, which suggests that detailed conditions of experiments, such as the spectrum of radiation, irradiance, exposure time, determine the outcome of the treatment. However, a wide range of immune cell studies have demonstrated that exposure to R/NIR most often has an anti-inflammatory effect. Finally, photobiomodulation molecular mechanism with particular attention to the role of interfacial water structure changes for cell physiology and regulation of the inflammatory process was described. Optimization of light parameters allows R/NIR to act as an anti-inflammatory agent in a wide range of medical applications.
Topics: Animals; Blood; Granulocytes; Humans; Inflammation; Infrared Rays
PubMed: 31170016
DOI: 10.1080/09553002.2019.1625464 -
Academic Radiology Sep 2022The purpose of this study was to evaluate the diagnostic performance of single-parameter, unimodal and bimodal magnetic resonance imaging (MRI) in differentiating tumor...
PURPOSE
The purpose of this study was to evaluate the diagnostic performance of single-parameter, unimodal and bimodal magnetic resonance imaging (MRI) in differentiating tumor recurrence (TR) from radiation necrosis (RN) in patients with glioblastoma (GBM) after treatment using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic susceptibility contrast enhancement-perfusion weighted imaging (DSC-PWI), and proton magnetic resonance spectroscopy (H-MRS).
MATERIALS AND METHODS
Patients with histologically proven GBM who underwent surgical intervention followed by chemoradiotherapy and developed a new, progressively enhanced lesion on follow-up MRI were included in our study. Subsequently, DWI, DTI, DSC-PWI, and H-MRS were performed. Then, these patients underwent a second surgical operation or follow-up MRI to prove TR or RN. MRI metrics include apparent diffusion coefficient (ADC) and relative ADC (rADC) values derived from DWI; fractional anisotropy (FA), axial diffusion coefficient (DA) and radial diffusion coefficient (DR) values derived from DTI; and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) derived from DSC-PWI. Spectral metabolites such as choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lactate (Lac), and lipids (Lip) were derived from MRS, and the ratios of these metabolites were calculated, including Cho/NAA, Cho/Cr, NAA/Cr, Lac/Cr, and Lip/Cr. These indices were compared between the TR group and RN group, and the receiver operating characteristic (ROC) curve was used to evaluate the performance in distinguishing TR from RN by using single-parameter, unimodal and bimodal MRI.
RESULTS
There were significant differences between the TR and RN groups in terms of ADC (p = 0.001), rADC (p < 0.001), FA (p = 0.001), DA (p = 0.003), DR (p = 0.003), rCBV (p < 0.001), rCBF (p < 0.001), Cho/NAA (p < 0.001), Lac/Cr (p < 0.001) and Lip/Cr (p < 0.001). ROC analysis suggested that rCBV, MRS, and DSC + MRS were the optimal single-parameter, unimodal, and bimodal MRI classifiers for distinguishing TR from RN, with AUC values of 0.909, 0.940, and 0.994, respectively.
CONCLUSION
The combination of parameters based on multiparametric MRI in the region of enhanced lesions is a valuable noninvasive tool for discriminating TR from RN.
Topics: Brain Neoplasms; Choline; Creatine; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Glioblastoma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Multiparametric Magnetic Resonance Imaging; Necrosis; Neoplasm Recurrence, Local; Radiation Injuries
PubMed: 34896001
DOI: 10.1016/j.acra.2021.11.008