Cerebral Radiation Research Articles

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

PurposeTo develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology.Methods and MaterialsMice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining.ResultsMRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001), and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001).ConclusionsFollowing GK irradiation, mice develop late time-to-onset cerebral RN histology mirroring clinical observations. MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score. This mouse model of RN will provide a platform for mechanism of action studies, the identification of imaging biomarkers of RN, and the development of clinical studies for improved mitigation and neuroprotection.

Stroke-like Migraine Attacks after Radiation Therapy Syndrome.

Objective:To summarize the clinical presentation, pathogenesis, neuroimaging, treatment, and outcome of stroke-like migraine attacks after radiation therapy (SMART) syndrome, and to propose diagnostic criteria for this disorder.Data Sources:We searched the PubMed database for articles in English published from 1995 to 2015 using the terms of “stroke-like AND migraine AND radiation.” Reference lists of the identified articles and reviews were used to retrieve additional articles.Study Selection:Data and articles related to late-onset effects of cerebral radiation were selected and reviewed.Results:SMART is a rare condition that involves complex migraines with focal neurologic deficits following cranial irradiation for central nervous system malignancies. The recovery, which ranges from hours to days to weeks, can be partial or complete. We propose the following diagnostic criteria for SMART: (1) Remote history of therapeutic external beam cranial irradiation for malignancy; (2) prolonged, reversible clinical manifestations mostly years after irradiation, which may include migraine, seizures, hemiparesis, hemisensory deficits, visuospatial defect, aphasia, confusion and so on; (3) reversible, transient, unilateral cortical gadolinium enhancement correlative abnormal T2 and fluid-attenuated inversion recovery signal of the affected cerebral region; (4) eventual complete or partial recovery, the length of duration of recovery ranging from hours to days to weeks; (5) no evidence of residual or recurrent tumor; (6) not attributable to another disease. To date, no specific treatment has been identified for this syndrome.Conclusions:SMART is an extremely rare delayed complication of brain irradiation. However, improvements in cancer survival rates have resulted in a rise in its frequency. Hence, awareness and recognition of the syndrome is important to make a rapid diagnosis and avoid aggressive interventions such as brain biopsy and cerebral angiography.

Treatment of Cerebral Radiation Necrosis With Bevacizumab

Cerebral radiation necrosis (RN) is a devastating complication of radiation therapy for brain tumors. Recent studies have explored the role of bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor in the treatment of RN of the brain. We report 24 patients with cerebral RN who were treated with bevacizumab. Twenty-four patients diagnosed with cerebral RN and treated with different schedules of bevacizumab between July 2007 and June 2012, were identified from the Cleveland Clinic Brain Tumor and Neuro-Oncology Center's database. Pretreatment and posttreatment magnetic resonance imaging (MRI) studies were compared to evaluate bevacizumab efficacy. Posttreatment MRI demonstrated a radiographic improvement in 23 of 24 patients on the postcontrast T1-weighted MRI and fluid-attenuated inversion-recovery sequences. Using the McDonald criteria, the average change in the T1-weighted postcontrast MRI was a decrease of 48.1%, and the average change in the fluid-attenuated inversion-recovery images was a decrease of 53.7%. There was a mean daily dose reduction of 9.4 mg of dexamethasone after initiation of bevacizumab in patients who were on steroids at the start of bevaciuzmab therapy for RN. Treatment with bevacizumab was well tolerated with only 1 grade 3 adverse event. The current study demonstrates that bevacizumab treatment results in excellent clinical and radiologic response in patients with RN caused by common forms of radiation therapy. The safety profile of bevacizumab use in RN is acceptable. In the current study, we found no difference between different schedules of bevacizumab in treatment outcomes.

Miliaire cérébrale carcinomateuse secondaire a un adénocarcinome pulmonaire muté EGFR

Miliary brain metastases are a rare form of brain metastatic lesions. We report the case of a 58-year-old patient with lung adenocarcinoma and an EGFR mutation, who had metastatic lesions in the bones, pleura and pericardia at the time of diagnosis. The patient was treated with tyrosine kinase inhibitor. A few months later, he presented with progressive neuropsychiatric symptoms, which were attributed to miliary brain metastases based on the radiological pattern (micronodules, some of which were calcified) and the elimination of alternative possible diagnoses. Despite tumour stability in the thorax and metastatic sites other than the brain, his neurological condition deteriorated, even after cerebral radiotherapy, leading to his death eight months after the diagnosis of lung cancer. Miliary brain metastases are a rare form of brain metastases with unusual clinical presentation. The diagnosis is based on the radiological pattern of cerebral miliary dissemination, with sometimes calcified tumor nodules. Despite its rarity, several cases have been reported in lung adenocarcinoma in the presence of EGFR mutations.

Necrosis cerebral por radiación: desafío diagnóstico y tratamiento clínico

Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies.

The syndrome of stroke-like migraine attacks after radiation therapy associated with prolonged unresponsiveness in an adult patient.

The syndrome of stroke-like migraine attacks after radiation therapy (SMART) is an extremely rare complication of cerebral irradiation. It is characterized by reversible episodic neurological dysfunction, commonly associated with headaches and occasionally with seizures, occurring years after cranial radiotherapy. Approximately a dozen cases have been reported in adult patients to date. In 1997, a 48-year-old man underwent resection of a right cerebellar metastasis from renal cell carcinoma, followed by whole-brain irradiation. Two years later he began experiencing recurrent episodes of headache associated with reversible left hemiparesis, dysphasia, visual field defects, and confusion. Over subsequent years these episodes increased in frequency, and in 2009 and 2010 the patient experienced 2 episodes associated with seizures and characterized by severe depression in level of consciousness (GCS 5); the latter of these was particularly prolonged, with neurological recovery requiring almost 6 months. Cortical and leptomeningeal gadolinium enhancement was demonstrated on magnetic resonance imaging during the second episode. Repeated electroencephalography studies did not demonstrate any epileptiform activity, and extensive workup including brain biopsy failed to identify any neoplastic, vascular, or infective pathology. The diagnosis of SMART syndrome was therefore made. Reduced level of consciousness of such severity and duration as observed here has not previously been described in SMART syndrome. This report, however, suggests that an excellent prognosis can be expected even in cases of prolonged unresponsiveness. The pathogenic mechanisms of SMART syndrome remain unclear, but may involve pathways common to both migraine and epilepsy.

In search of a treatment for radiation-induced optic neuropathy.

Radiation-induced optic neuropathy (RON) is an iatrogenic complication that causes severe, irreversible vision loss in one or both eyes within the months to years following radiation therapy. Posterior RON is a rare but devastating toxicity of radiation applied to the visual pathways to treat paranasal sinus and skull base tumors. Anterior RON is an unavoidable consequence of proton beam irradiation or ophthalmic plaque treatment of orbital, choroidal, or retinal tumors. Various treatments aimed at stabilizing and ideally reversing vision loss have been investigated but only in small cases series. Systemic corticosteroids and anticoagulants, which are moderately effective when used for cerebral radiation necrosis, have shown no signs of benefit for RON. Hyperbaric oxygen therapy may promote short-term, partial recovery of vision in select patients, especially at partial pressures of at least 2.4 atm and when administered early after symptom onset. Reversal of visual deficits through treatment with systemic bevacizumab has been reported, but until controlled studies are performed, the side effect profile of stroke and myocardial infarction should limit its use in a population with predisposing cardiovascular risk factors. Intravitreal bevacizumab has shown promising results in patients with anterior RON, but repeated, long-term injections are required for sustained effect. As no intervention has been clearly shown to halt or reverse vision loss, larger prospective studies are needed to validate observed benefits for any of the treatments that have been described.

NI-28 * ANALYSIS OF BEVACIZUMAB RESPONSE TO DISTINGUISH BETWEEN TUMOR RECURRENCE AND CEREBRAL RADIATION NECROSIS

OBJECTIVE: Recurrent malignant gliomas are the disease stage difficult to control progressive tumor (PT). Most of them has a treatment history of radiotherapy and there are more than a few lesion with a component of cerebral radiation necrosis (RN) (Fujimoto, 2013). Bevacizumab (BEV) is a possible therapeutic option for RN as well as recurrent malignant glioma. In this study, we investigate the components of PT and RN in patients with recurrent malignant glioma by image analysis before and after administration of BEV. PATIENTS AND METHODS: Six patients with malignant glioma had been treated with radiation therapy. Their disease progression were identified, which contained a component of RN detected by MRI and 11C-methionine-PET (met-PET). All patients received BEV 5mg/kg every 2 week. We analyzed the lesion with MRI and met-PET. RESULTS: The enhanced lesions with high uptake (SUV > 1.8) in met-PET got decreased enhancement and stable apparent diffusion coefficient (ADC) value after BEV treatment, in which tumor recurrence appeared to occur. The enhanced lesions with low uptake (SUV < 1.8) in met-PET decreased both their enhancement and ADC value, in which no tumor recurrence was identified. CONCLUSION: It is difficult to distinguish between PT and RN because of both lesions have similar findings on MRI. Our findings suggests that the enhanced lesion decreasing ADC value followed by BEV mainly consists of RN. The changes of ADC value by BEV may be concerned with the declining neovascularity and interstitial edema.

SM-01 * APPLICATION OF BEVACIZUMAB TO POST-IRRADIATED CEREBRAL LESION: DIAGNOSIS, INTERVENTION AND OUTCOME

BACKGROUND: Taking results of AVAglio (Chinot et al., 2014), BRAIN study (Friedman et al., 2009) and JO22506 (Nagane et al., 2012), bevacizumab (BEV) had been approved for the treatment of newly diagnosed and recurrent malignant glioma. In addition, there are some trials using BEV for symptomatic cerebral radiation necrosis (RN, Levin et al., 2011) and other brain tumor (e.g. meningioma) patients. METHODS: We retrospectively analyzed 10 cases (median age: 59.5 [range 26-69]) of cerebral lesion occurred after irradiation. By the combination of diagnostic imaging (MRI and PET) and clinical course, they were diagnosed as RN. Primary irradiated lesions were as below: 5-case of metastatic brain tumor, 2-case of meningioma and 3-case of other primary head and neck tumor. These patients were administered six cycles of 5 mg/kg bevacizumab every two weeks. RESULTS: In 7 cases, planned 6-cycles of BEV had been finished. In 3 of these 7 cases, wound complication or (extracranial) hemorrhage was clinically treated. In another 3 cases, BEV were ceased: disease progression, fetal hemorrhagic complication and deterioration of performance status respectively. After the BEV treatment, 3 cases were diagnosed as tumor recurrence by surgical resection of treated lesions. DISCUSSION: Diagnosis of RN is so difficult; we must pay attention to possibility of tumor recurrence. On the other hand, BEV could improve clinically and radiologically cerebral edema induced by RN and tumor progression. We had better consider application of BEV to post-irradiated cerebral lesion, case by case.

CN-04 * TREATMENT OF PEDIATRIC CEREBRAL RADIATION NECROSIS: A META-ANALYSIS

BACKGROUND: Cerebral radiation necrosis (CRN) is a well-characterized toxicity of radiation therapy that can result in significant neurologic deficits and be life threatening. Treatment for CRN has included surgical resection, corticosteroids, hyperbaric oxygen therapy (HBOT), and bevacizumab among other modalities, but no consensus approach has been identified. Given the paucity of pediatric CRN data, we sought to codify the approaches to treatment of radiation necrosis in pediatric patients. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid MEDLINE were searched to identify all relevant pediatric reports. RESULTS: Thirty-one pediatric patients, twenty-six with primary central nervous system tumors and four with arteriovenous malformations developed CRN, diagnosed by characteristic MRI findings, most (n = 28) with accompanying neurologic deficits. Patients received treatment with steroids alone (n = 5) or steroids followed by bevacizumab (n = 11) or HBOT (n = 12). Three asymptomatic patients did not receive intervention. 10/11 patients treated with steroids and bevacizumab, and 11/12 treated with steroids and HBOT improved. In all cases of steroid-resistent CRN, addition of bevacizumab induced improvement except in one case of disease progression. One patient treated with steroids alone died with progressive neurologic deterioration. With the exception of steroid-related adverse events, there were no reported significant side effects. CONCLUSIONS: Due to the small numbers of pediatric patients with CRN, analysis of treatment modalities is confined to limited reports. Furthermore, cases of CRN are likely underreported as we have seen much higher rates of CRN than the 3-5% reported in the literature at our institution in the past five years. The most common treatment following steroid initiation is addition of either bevacizumab or HBOT with good success. However, larger randomized controlled trials are needed to establish a definitive treatment algorithm that can be applied to children affected by CRN.

Radiothérapie d’une tumeur gliale chez une femme enceinte : évaluation de la dose fœtale en irradiation conformationelle tridimensionnelle ou avec modulation d’intensité

The purpose was to assess three treatments planning techniques including one in intensity-modulated radiation therapy (IMRT) for cerebral irradiation of pregnant woman, in order to limit the dose delivered to the foetus. The treatment provided was 60Gy to the planning target volume. Estimated foetal dose was measured using an anthropomorphic phantom, on the upper and middle part of the uterus. The first plan consisted in four beams in conformational technique delivered from a Varian accelerator with a 120 leaves collimator, the second one used non-coplanar fields and the third one assessed IMRT. With the conformational technique, the dose at the upper part of the uterus was 8.3mGy and 6.3mGy at the middle part. The dose delivered to the foetus was higher with the non-coplanar fields. In IMRT, the dose at the upper part of the uterus was 23.8mGy and 14.3mGy at the middle part. The three plans used 6MV X-rays. Because of the use of leaves and non-coplanar fields, IMRT does not seem to be the optimal technique for the treatment of pregnant woman. However, the dose delivered to the foetus remains low and below the dose of 100mGy recommended by the International Commission of Radiological Protection. It seems possible to consider the use of this technique for a better sparing of organs at risk for the mother.

Effect of cerebral X-ray irradiation on learning and memory function in young SD rats

To investigate the effect of cerebral X-ray irradiation on learning and memory function in young rats. Fifty-four SD rats aged 35 d were randomly divided into 3 groups with 18 in each group: rats in 3-d group and 7-d group received X-ray irradiation with a dose of 28.5 mGy/d for 3 d and 7 d, respectively; rats in control group received sham X-ray irradiation. Morris water maze (MWM) was tested when animals at age of 60 d; then the animals were sacrificed and brain samples were taken. The neurodegeneration was observed by Fluro-Jade B staining; the expression of N-methyl-aspartate (NMDA) receptors subunit 2B (NR2B) and postsynaptic density protein-95 (PSD-95) in the hippocampus were analyzed by immunofluorescence and Western blot methods, respectively, and ultrastructure of CA1 region was observed with electron microscopy. No significant difference in 1-4 d escape latency as shown in MWM test was noted between 3d group and control group (P>0.05); while the escape latency in 7d group was significantly longer than that in control group (P<0.01). No significant differences in lingering in the quadrant and the frequency of passing through the original platform between 3-d group and control group (P>0.05), while those in 7-d group were significantly lower than those in control group (P<0.01). Compared to control group, the number of FJB positive cells in 7-d group was increased (P<0.01); the expressions of NR2B and PSD-95 in hippocampus CA1 region were also increased (P<0.05). The ultrastructure observation in 7-d group showed that the synapse structure of some neurons was impaired. X-ray irradiation may affect learning and memory function of young rats, which is associated with overexpression of NR2B and PSD-95 in hippocampal regions.

Carcinomes bronchiques à petites cellules limités : traitement standard et nouvelles approches thérapeutiques

Small cell carcinomas are aggressive on account of their high and early risk of dissemination. They represent less than 20 % of all lung cancers and only a third of these patients present limited stage disease at diagnosis. Currently, treatment is based on conformational thoracic irradiation and chemotherapy combining platinum and etoposide. Because of the high risk of brain metastases, prophylactic cranial irradiation (PCI) is indicated in patients with a complete response in limited disease. Progress is the consequence of a better combination of thoracic and cerebral irradiation with poly chemotherapy. Many issues are subject to further clinical research concerning systemic treatment which is the pivotal treatment, modalities of combination radio-chemotherapy, radiotherapy target volumes, optimum dose and drugs used in association with irradiation. New approaches such as immune therapy should be evaluated.

P06.03 * CASE REPORT OF A METASTASIS OF SQUAMOUS CELL LUNG CARCINOMA INTO AN INTRACRANIAL MENINGIOMA

INTRODUCTION: Rare cases of tumor-to-meningioma metastases have yet been reported before. Cancer metastasis into a meningioma is a rare and often incidential finding. The most commonly reported malignancies are breast and lung cancer. Meningiomas are the most common intracranial lesion to host metastatic tissue and meningiomas seem to provide a favorable environment for metastatic seeding. Several factors responsible for tumor metastasis into meningioma have been proposed :meningiomas are highly vascular and also grow slowly. In addition their high collagen and lipid content seems to be supportive to the seeding and growing of malignant cells. Also, meningeomas express binding proteins which may also play a role in metastatic seeding. CASE REPORT: A 73-year-old woman was admitted because of progression with a 3-week history of her former of left sided arm weakness. She had undergone a right upper lobectomy for poorly differentiated sqamous cell carcinoma of the lung 3 months ago. An MRI scan of the brain revealed a lesion the size of 3.5 cm on the right parietal side. It was adhering to the dura mater, which suggested an extraaxial origin of the tumor and meningeoma was suggested. The lesion showed significant contrast agent uptake and was surrounded by peritumoral edema. A surgical removal of the lesion was performed. Histologic analysis showed a secretory meningioma (WHO grade I) highly infiltrated with metastatic cancer cells of a poor-differentiated squamous cell carcinoma. The focus within the meningeoma stained positive for p16, CK 5/6, p63/HMW-CK, CK AE 1/3 and negative for TTF-1, Ki-67. The patient was treated with postoperative cerebral radiation theraphy. A CT staging of the chest and abdomen was performed and revealed new blastomatoid lesions of the lung, liver and the left adrenal gland. The general condition of the patient deteriorated fast in the following weeks and she died two months after surgery as a result of the reactivation of the malignant squamous cell lung carcinoma. DISCUSSION: The phenomenon of tumor to tumor metastasis is defined by two criteria: The metastatic focus must be encased by a rim of histologically distinct tumor tissue and a proven primary carcinoma that is compatible with the metastasis. In this patient, an intracranial meningeoma was the target for the seeding of a malignant systemic cancer. Given the comparatively large number of patients with meningeoma and even larger number of persons with cancer this coincidence could be seen higher than reported. The practical issue is to identify future factors to identify patients with cancer metastasis into meningioma to improve therapeutic strategies.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain metastases and underwent salvage CyberKnife treatment. Recurrent edema and emerging radiation necrosis were not observed. CyberKnife radiosurgery followed by early use of bevacizumab is promising and appears safe for treatment of brain metastases with extensive cerebral edema.

The Pathophysiology of Cerebral Radiation Necrosis and the Role of Laser Interstitial Thermal Therapy

tereotactic radiosurgery can effectively ablate brain tumors; however, it also has the potential to cause tissue S injury around the tumor site. The acute effects on the brain tissue are usually reversible; they occur <2 months after radiotherapy and result from endothelial cell apoptosis, which causes disruption of the blood-brain barrier and peritumoral edema (20, 22, 33). Acute radiation injury also incites inflammatory pathways, which are accelerated by chronic hypoxia secondary to endothelial remodeling, further setting the stage for “microenvironmental change” (33). If this process continues to evolve, the result is irreversible cerebral radiation necrosis (RN).

Bevacizumab treatment in malignant meningioma with additional radiation necrosis

Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. We report the case of an 80-year-old woman who underwent bevacizumab therapy (5mg/kg every 2weeks for 2months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) gradeIII. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma.

The diagnostic properties of frozen sections in suspected intracranial tumors: A study of 578 consecutive cases.

Background:Intraoperative frozen section (FS) diagnostics is an important diagnostic tool in neurosurgery, but agreement with final histopathology diagnoses may vary. In the present study we assess the diagnostic properties of intraoperative FSs in suspected intracranial tumors.Methods:Retrospective single-center review of consecutive patients with suspected intracranial brain tumors from January 2008 to December 2012. We included all cases were both an intraoperative FS and a formalin-fixed paraffin-embedded (FFPE) section had been acquired. Agreement with final diagnosis, sensitivity, specificity, and predictive values were explored. Time between date of surgery and first final diagnosis based on FFPE section, whether the patients had undergone previous brain surgery and/or prior cerebral radiotherapy were also registered.Results:Agreement between FS diagnoses and final FFPE section diagnoses was seen in 504/558 (90.3%), while there was lack of agreement in 54/558 (9.7%). In 20 cases, agreement was not classifiable. Agreement was lower in low-grade gliomas (82.5%) than in high-grade gliomas (93.2%). Agreement between FS and FFPE was significantly higher in primary operations (92.1%) than in re-do operations (81.5%) (P = 0.001). Sensitivity of FS ranged from 30.8% in lymphomas to 94.6% in meningiomas.Conclusions:Intraoperative FS diagnoses demonstrate high diagnostic accuracy. However, agreement varies among histopathological entities and is lower in low-grade tumors than in high-grade tumors. Sensitivity for diagnosing CNS lymphomas is low. A variable degree of reservation is always necessary when interpreting and communicating FS diagnoses.

Delayed cerebral radiation necrosis after neutron beam radiation of a parotid adenocarcinoma: a case report and review of the literature.

Cerebral radiation necrosis (CRN) is a well described possible complication of radiation for treatment of intracranial pathology. However, CRN as sequelae of radiation to extracranial sites is rare. Neutron beam radiation is a highly potent form of radiotherapy that may be used to treat malignant tumors of the salivary glands. This report describes a patient who underwent neutron beam radiation for a parotid adenocarcinoma and who developed biopsy-confirmed temporal lobe radiation necrosis thirty months later. This represents the longest time interval described to date, from initial neutron radiation for extracranial pathology to development of CRN. Two other detailed case studies exist in the literature and are described in this report. These reports as well as our patient's case are reviewed, and additional recommendations are made to minimize the development of CRN after extracranial neutron beam radiation. Physicians should include the possible diagnosis of CRN in any patient with new neurologic signs or symptoms and a history of head and neck radiation that included planned fields extending to the base of the skull. Counseling of patients prior to neutron beam radiation should include potential neurologic complications associated with CRN and risks of treatment for CRN including neurosurgical intervention.

Quality of patient positioning during cerebral tomotherapy irradiation using different mask systems

Patient immobilization during brain tumor radiotherapy is achieved by employing different mask systems. Two innovative mask systems were developed to minimize the problems of claustrophobic patients. Our aim was to evaluate whether the quality of patient immobilization using the new mask systems was equivalent to the standard mask system currently in use. Thirty-three patients with cerebral target volumes were irradiated using the Hi-Art II tomotherapy system between 2010 and 2012. Each group of 11patients was fitted with one of the two new mask systems (Crystal® or Open Face® mask, Orfit) or the standard three-point mask (Raycast®-HP, Orfit) and a total of 557 radiotherapy fractions were evaluated. After positioning was checked by MV-CT, the necessary table adjustments were noted. Data were analyzed by comparing the groups, and safety margins were calculated for nonimage-guided irradiation. The mean values of the table adjustments were: (a) lateral (mm): - 0.22 (mask 1, standard deviation (σ): 2.15); 1.1 (mask 2, σ: 2.4); - 0.64 (mask 3, σ: 2.9); (b) longitudinal (mm): - 1 (mask 1, σ: 2.57); - 0.5 (mask 2, σ: 4.7); - 1.22 (mask 3, σ: 2.52); (c) vertical (mm): 0.62 (mask 1, σ: 0.63); 1.2 (mask 2, σ: 1.0); 0.57 (mask 3, σ: 0.28); (d) roll: 0.35° (mask 1, σ: 0.75); 0° (mask 2, σ: 0.8); 0.02° (mask 3, σ: 1.12). The outcomes suggest necessary safety margins of 5.49-7.38mm (lateral), 5.4-6.56mm (longitudinal), 0.82-3.9mm (vertical), and 1.93-4.5° (roll). There were no significant differences between the groups. The new mask systems improve patient comfort while providing consistent patient positioning.