Cerebral Radionecrosis Research Articles

Radionecrosis of the Anterior Skull Base as a Consequence of Sinonasal Malignant Tumor Management: Diagnosis, Prevention, and Management

Objectives: Treatment of sinonasal malignant tumors is based on surgery followed by radiotherapy, and eventually combined with chemotherapy. A late complication of this treatment is cerebral radionecrosis. The aims of this study are to: (1) highlight the main diagnosis criteria of radionecrosis, (2) identify any risk factors, and (3) determine methods of prevention.

Progressive enlargement of a mass lesion in late cerebral radionecrosis

The progressive enlargement of a mass lesion in late cerebral radionecrosis (LCR) was studied using a surgical specimen from a woman’s irradiated brain. Using immunohistochemical (IHC) staining on paraffin-embedded sections, expression of tumor necrosis factor-alpha (TNFα), interleukin (IL)6, Flk-1, and vascular endothelial growth factor (VEGF) was semi-quantitatively evaluated in the necrotic area and areas distant and adjacent to the necrotic area. High immunoreactivity for TNFα, IL6, and VEGF in regions distant to the necrotic core were strongly associated with inflammatory cell density, hyalinized vessels, and vascularization. Ghost cells stained with glial fibrillary acidic protein (GFAP), Ki-M1P, KP-1, ubiquitin-C-terminal hydrolase 1, and fibrinoid necrosis were observed in the necrotic area and adjacent regions. These results suggest that necrotic factors, inflammatory reaction, and angiogenetic factors act temporally and spatially through radiation-induced vascular endothelial cell damage to contribute to the progressive enlargement of an enhancing mass lesion in LCR.

Le bévacizumab dans le traitement des radionécroses cérébrales

Bevacizumab is a monoclonal antibody, which neutralizes the effect of vascular endothelium growth factor (VEGF) allowing regression of tumour vessels and a decrease in the permeability of the blood-brain barrier. Already used in oncology as adjuvant treatment for certain metastatic cancers and in second line for high-grade gliomas, it has been recently used as a treatment of cerebral radionecrosis resisting conventional drug treatment and hyperbaric oxygen. This article presents three patients with cerebral radionecrosis and treated by monthly infusions of bevacizumab (10 mg/kg per month). The patients had developed cerebral radionecrosis after radiation therapy for a malignant brain tumour. The radionecrosis was proved by magnetic resonance imaging and spectroscopy. The first patient received only one perfusion of bevacizumab, as the development of a lymphopenia prevented the patient from continuing with the treatment. The second patient received four infusions, but the absence of improvement of the clinical symptoms and progression of the radiolesion led to discontinuation of the treatment. The third patient developed several severe side effects, a transient ischemic accident and a perforated corneal ulcer, resulting again in premature discontinuation of treatment. The development of severe side effects, combined with the absence of notable clinical and radiologic improvements resulting from the use of bevacizumab as a treatment resulted in the premature interruption of such treatment, in all three patients.

Preliminary Calculation of RBE-weighted Dose Distribution for Cerebral Radionecrosis in Carbon-ion Treatment Planning

Cerebral radionecrosis is a significant side effect in radiotherapy for brain cancer. The purpose of this study is to calculate the relative biological effectiveness (RBE) of carbon-ion beams on brain cells and to show RBE-weighted dose distributions for cerebral radionecrosis speculation in a carbon-ion treatment planning system. The RBE value of the radionecrosis for the carbon-ion beam is calculated by the modified microdosimetric kinetic model on the assumption of a typical clinical α/β ratio of 2 Gy for cerebral radionecrosis in X-rays. This calculation method for the RBE-weighted dose is built into the treatment planning system for the carbon-ion radiotherapy. The RBE-weighted dose distributions are calculated on computed tomography (CT) images of four patients who had been treated by carbon-ion radiotherapy for astrocytoma (WHO grade 2) and who suffered from necrosis around the target areas. The necrotic areas were detected by brain scans via magnetic resonance imaging (MRI) after the treatment irradiation. The detected necrotic areas are easily found near high RBE-weighted dose regions. The visual comparison between the RBE-weighted dose distribution and the necrosis region indicates that the RBE-weighted dose distribution will be helpful information for the prediction of radionecrosis areas after carbon-ion radiotherapy.

Results of excision of cerebral radionecrosis: experience in patients treated with radiation therapy for nasopharyngeal carcinoma

In theory, the purpose of the treatment of cerebral radionecrosis (CRN), a nonneoplastic condition, is to minimize loss of brain function by preventing the progression and reversing some of the processes of CRN. In a practical sense, factors for achieving this purpose may include the following: removal of a CRN lesion that is causing mass effect, control of brain edema, prevention of recurrence of CRN lesions, minimization of adverse effects from treatments, and achievement of reasonably long and good-quality survivals. Based on these practical issues, the authors performed a retrospective study to evaluate the results of excision for the treatment of CRN. The authors retrospectively reviewed the results of excision of CRN lesions in a group of patients with temporal lobe CRN due to radiotherapy for nasopharyngeal carcinoma. Patients who had undergone surgery at the authors' institution between January 1998 and November 2008 were analyzed. Surgical results were evaluated by assessing postoperative resolution of brain edema, recurrence of temporal lobe CRN, surgery-related complications, and postoperative functional status and survival. Twenty-four patients were included (age range 39-69 years; in 23 patients nasopharyngeal carcinoma was in remission). All patients underwent craniotomy for excision of the contrast-enhancing region. The indications for operation were temporal lobe CRN lesions with a mass-occupying effect beyond the temporal lobe. There were 32 craniotomies in all (mean postoperative follow-up 40 months). It was found that brain edema resolved rapidly postoperatively. The recurrence and reoperation rates were 6.3 and 3.1%, respectively. There were no surgery-related deaths. The median survival was 72 months, and 67% of the patients had a Karnofsky Performance Scale score of > or = 70% at the time of their last follow-up. In a specific group of patients with CRN of the temporal lobe in whom the CRN lesions were causing a mass-occupying effect beyond the temporal lobe, excision of the contrast-enhancing region was safe and could achieve prompt resolution of brain edema and a low incidence of recurrence of CRN.

Cerebral radio-necrosis in a patient with pseudo-tumoral multiple sclerosis

A pseudo-tumoral course of multiple sclerosis is very rare. In the paper, a morphologically confirmed case of multiple sclerosis with a pseudo-tumoral course is described. A radiation treatment (because of a misdiagnosis of cerebral tumor) resulted in radio-necrosis of the cerebral tissue. Presented are the experience of treatment of this patient, differential diagnosis and efficacy of the long-term hormone therapy.

Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis

Cerebral radiation necrosis is a serious complication of radiation treatment for brain tumors. Therapeutic options include corticosteroids, anticoagulation and hyperbaric oxygen with limited efficacy. Bevacizumab, an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis. We retrospectively reviewed 6 patients with biopsy proven cerebral radiation necrosis treated with bevacizumab between 2006 and 2008. Interval MRI follow-up demonstrated radiographic response in all patients with an average reduction of 79% for the post gadolinium studies and 49% for the FLAIR images. The initial partial radiographic response was noted for up to a mean follow-up time of 5.9 months (6 weeks to 18 months). Bevacizumab appears to produce radiographic response and clinical benefits in the treatment of patients with cerebral radionecrosis.

Epileptic seizures caused by encephalomalasic cysts following radiotherapy: a case report

IntroductionCerebral radionecrosis is a delayed and rarely observed complication of radiotherapy. Cerebral radionecrosis may occur as cystic encephalomalasic formations which cover the intracranial region. These cysts may, in rare cases, become quite large. They may cause drug-resistant seizures, neurological deficits and consciousness disorders.Case presentationA 55-year-old, Turkish female patient was admitted to hospital with seizure, consciousness disorder and weakness in the right side of her body. The patient had history of an operation in the left maxillary area due to basal cell carcinoma 7 years previously and then history of radiotherapy due to relapse 2 years later the operation. The patient had large cystic encephalomalasic lesions. Despite steroid and dual antiepileptic treatments, the patient's complaints had significantly worsened and seizures continued. Surgical treatment resulted in a significant improvement.ConclusionThis report underlines the significance of surgery in cerebral radionecrosis treatment in well-selected cases using appropriate approaches.

Pathological review of late cerebral radionecrosis

Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and GFAP-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions.

Radionécrose cérébrale chez les patients irradiés pour cancer du nasopharynx : à propos de neuf cas

Purpose To study the clinical, radiological, therapeutic and progressive aspects of brain radionecrosis after treatment for nasopharyngeal carcinoma. Patients and methods Nine patients (seven men and two women) of mean age 47.7 years old (extremes: 18–57 years old) were treated for UCNT (undifferentiated carcinoma of the nasopharynx) between 1989 and 2003 and developed cerebral radionecrosis. All patients were treated with radical radiotherapy. The mean total dose was 73.5 Gy (70–75 Gy). Dose per fraction was 2 to 2.5 Gy, one fraction daily. One patient received adjuvant brachytherapy to the dose of 8 Gy and four patients also received chemotherapy. Results Brain radionecrosis was authenticated by brain imaging (CT scan ± MRI): the imaging was ordered in seven cases to elucidate non-specific neurological signs and two cases were discovered fortuitously. The time to the appearance of neurological signs was 40.3 months (10 to 108 months). The localization was temporal in six cases, parieto-occipital (one case) and bulbomedullar (two cases). After a mean follow-up period of 30.6 months (12–84 months), clinical outcomes were favorable in all cases receiving medical treatment (corticoids), with a stabilization of the radiological lesions in eight cases and complete radiological regression in one patient. Conclusion Brain radionecrosis is a late complication rarely occurring in patients irradiated for UCNT. Imaging techniques (CT scan but more so MRI) play a major role in the diagnosis. Corticotherapy resulted in a durable objective response in all patients and, in most cases, resulted in radiological stabilization.

Cerebral Radionecrosis in Patients with Nasopharyngeal Carcinoma

This study involved seven patients with cerebral radionecrosis following radiation therapy for nasopharyngeal carcinoma (NPC). Their charts were reviewed and the relationship of extracranial malignancies to cerebral radionecrosis was investigated. The radiation dose ranged from 70 to 135 Gy, and the latency was from 6 to 39 months. Two of seven patients died of NPC-related complications during follow-up. The crude incidence of cerebral radionecrosis in patients with NPC was 0.93% in our series. Improvement of symptoms could be achieved by corticosteroid therapy, with or without surgery. In a review of the literature, there were 306 cases of cerebral radionecrosis in extracranial malignancies. The nasopharynx is the most common primary site in cerebral radionecrosis of extracranial malignancies, followed by the scalp and sinonasal tract. The 3-year overall survival rate in our series was 68.57%, as provided by the Kaplan-Meier product limited method. Cerebral radionecrosis in NPC patients should be differentiated from tumor recurrence, in order to apply the appropriate treatment.

Potential usefulness of Tl-201 SPECT for differentiating radionecrosis in an irradiated nasopharyngeal carcinoma patient

Differentiation between cerebral radionecrosis and intracranial relapse in irradiated nasopharyngeal carcinoma (NPC) patients challenges the clinicians, especially when clinical manifestation and MRI findings are inconclusive. A 63-year-old NPC patient had intermittent dizziness and unsteady gait 3 years after irradiation. An ice water caloric test revealed absent response on the right ear, which was compatible with an enhanced lesion at the right temporal lobe on MRI scan. Furthermore, abnormal focally increased uptake over the anteriomedial aspect of the right temporal lobe was disclosed on 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET), which suggested intracranial relapse. Conversely, serological study for Epstein-Barr viral titer was within normal limits, arguing against either recurrent or metastatic NPC. Hence, thallium (Tl)-201 single photon emission computed tomography (SPECT) was subsequently conducted, which failed to demonstrate abnormal thallium accumulation in the corresponding area. Accordingly, radiation necrosis of the temporal lobe rather than intracranial relapse is considered. The patient was rather well without locoregional recurrence or distant metastasis 2 years after presentation.

Radiation-induced brain disorders in patients with pituitary tumours.

Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 +/- 8.3; median, 36) with a follow-up period of 6-96 months (mean, 18.3 +/- 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 +/- 13.4; median, 45), which was given in 15-30 fractions (mean, 18.6 +/- 5.0; median, 15) with 2.8 +/- 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 +/- 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 +/- 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously.

Cerebral Radionecrosis with Cystic Degeneration Following Radiotherapy for Nasal Cavity Squamous Cell Carcinoma: A Case Report

A 31-year-old man with nasal cavity squamous cell carcinoma was treated in our hospital with two courses of radiotherapy (120 Gy total dose) followed by surgical tumor resection. Three years after the last irradiation, he developed seizures as well as changes in behavior and consciousness. Medical therapy with diphenylhydantoin (Dilantin) terminated the seizures. Dysphagia, unsteady gait, and right-side limb weakness developed 37 months after the onset of seizures. Magnetic resonance imaging showed a large, cystic mass in the left temporal lobe with left to right midline shift. Following craniotomy with decompression of the cystic mass, the patient improved clinically. No malignant cells were found in the specimen. No further progression of neurologic symptoms was noted after a 1-year follow-up. Cerebral radionecrosis is an uncommon late complication of radiotherapy and needs to be differentiated from tumor recurrence or metastasis if the irradiation field covers the cerebral region in patients with head and neck malignancies.

Cerebral radionecrosis following the treatment of parotid tumours: a case report and review of the literature

Radiotherapy is an accepted part of the treatment of malignant tumours of the parotid gland. The use of radiotherapy in benign parotid tumours, where spillage of tumour cells has occurred at operation, is more controversial. Radiotherapy to the parotid bed is not without morbidity. Complications may arise as a result of radiation damage to neighbouring structures and there is also potential to induce malignant disease. A patient, whose postoperative radiotherapy following resection of a pleomorphic salivary gland adenoma was complicated by cerebral necrosis, is discussed. The literature pertaining to morbidity of radiotherapy for parotid tumours is reviewed.

Cerebral radionecrosis following the treatment of parotid tumours: a case report and review of the literature

Radiotherapy is an accepted part of the treatment of malignant tumours of the parotid gland. The use of radiotherapy in benign parotid tumours, where spillage of tumour cells has occurred at operation, is more controversial. Radiotherapy to the parotid bed is not without morbidity. Complications may arise as a result of radiation damage to neighbouring structures and there is also potential to induce malignant disease. A patient, whose postoperative radiotherapy following resection of a pleomorphic salivary gland adenoma was complicated by cerebral necrosis, is discussed. The literature pertaining to morbidity of radiotherapy for parotid tumours is reviewed.

The Role of 99mTc HMPAO Functional Brain Imaging in Detection of Cerebral Radionecrosis

Dadparvar, Simin M.D.; Wang, Jingbo M.D.; Gillan, Muhammad M. M.D.; Bartolic, Edward Ph.D.; Koffler, Sandra P. Ph.D.; Minard, Traci L.; Walter, R. N.; Slizofski, J. M.D.; Miyamoto, Curtis M.D. Author Information

Treatment of radiation‐induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.

Apoplectic intracerebral hemorrhage: An unusual complication of cerebral radiation necrosis

A patient with apoplectic intracerebral hemorrhage from delayed cerebral radionecrosis is reported. The histological changes of abnormal telangiectatic vessels account for the unusual clinical presentation. The pathogenesis and treatment of radionecrosis are discussed, and massive hemorrhage as a complication is emphasized.

The risk of cerebral radionecrosis in relation to dose, time and fractionation. A follow-up study.

The risk of cerebral radionecrosis in relation to dose, time and fractionation. A follow-up study.