Treatment Of Radiation Necrosis Research Articles

Clinical Experience of Bevacizumab for Radiation Necrosis in Patients with Brain Metastasis.

BackgroundAs the application of radiotherapy to brain metastasis (BM) increases, the incidence of radiation necrosis (RN) as a late toxicity of radiotherapy also increases. However, no specific treatment for RN is indicated except long-term steroids. Here, we summarize the clinical results of bevacizumab (BEV) for RN.MethodsTen patients with RN who were treated with BEV monotherapy (7 mg/kg) were retrospectively reviewed. RN diagnosis was made using MRI with or without perfusion MRI. Radiological response was based on Response Assessment in Neuro-Oncology criteria for BM. The initial response was observed after 2 cycles every 2 weeks, and maintenance observed after 3 cycles every 3–6 weeks of increasing length intervals.ResultsThe initial response of gadolinium (Gd) enhancement diameter maintained stable disease (SD) in 9 patients, and 1 patient showed partial response (PR). The initial fluid-attenuated inversion recovery (FLAIR) response showed PR in 4 patients and SD in 6 patients. The best radiological response was observed in 9 patients. Gd enhancement response was 6 PR and 3 SD between 15–43 weeks. Reduction of FLAIR showed PR in 5 patients and SD in 4 patients. Clinical improvement was observed in all but 1 patient. Five patients were maintained on protocol with durable response up to 23 cycles. However, 2 patients stopped treatment due to primary cancer progression, 1 patient received surgical removal from tumor recurrence, and 1 patient changed to systemic chemotherapy for new BM. Grade 3 intractable hypertension occurred in 1 patient who had already received antihypertensive medication.ConclusionBEV treatment for RN from BM radiotherapy resulted in favorable radiological (60%) and clinical responses (90%). Side effects were expectable and controllable. We anticipate prospective clinical trials to verify the effect of BEV monotherapy for RN.

Bevacizumab efficacy in treatment of brain radiation necrosis

Radiation therapy (RT) plays an important role in treatment of primary and metastatic CNS tumors and some non-neopiastic conditions (arteriovenous malformations, trigeminal neuralgia). Radiation necrosis (RN) is a common adverse effect of RT. Until recently steroid therapy was used as a main treatment regimen for RN. Mechanisms of RN development are not clear; however, it was shown that vascular endothelial growth factor (VEGF) plays a critical role in its formation. A number of surveys showed efficacy of bevacizumab as an anti-VEGF agent in treatment of RN. Radiation necrosis pathogenesis, diagnostics and treatment are summarized in this review.

Bevacizumab for the treatment of radiation necrosis in melanoma patients.

e13548 Background: Radiation necrosis (RN) can be a late complication of radiotherapy for CNS malignancy, often associated with neurological morbidity. High dose corticosteroids or surgical resection have been the standard of care treatment (tx), but protracted steroid course can lead to significant side effects and surgery is not always feasable. While there is evidence that the anti-VEGF antibody bevacizumab (Bev) can be effective for RN in other cancer types, evidence supporting its use for RN in melanoma patients (pts) is lacking, due to known risk of spontaneous bleeding in melanoma brain metastasis (MBM) and increased bleeding risk with Bev. Methods: We retrospectively identified 6 melanoma pts who received Bev for RN, and demographics, systemic and radiation tx history were obtained. Diagnosis of RN was established by MRI in all pts, and pathology confirmed RN in one pt. Results: Description of the 6 pts identified are shown in Table 1. Conclusions: We present 6 melanoma pts who developed RN after CNS radiation and who were treated with 2-6 doses of Bev. None of these pts developed bleeding, and all pts experienced improvement in symptoms and quality of life, with concurrent improvement of imaging in 5 pts. Our series suggests that in selected melanoma pts Bev may be a safe and effective treatment for RN for MBM and should be evaluated in a prospective setting. [Table: see text]

Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature.

Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords “radiation necrosis”, “radiotherapy” and “bevacizumab” alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy.

Management of Cerebral Radiation Necrosis: A Retrospective Study of 12 Patients.

Cerebral radiation necrosis (RN) is a severe complication of radiotherapy for cerebral pathologies. This study discusses the radiographic and pathological features of 12 patients with RN and investigates the management strategy. Eleven patients with brain tumors, and one with cerebral cavernous angioma, treated by surgical resection or Gamma Knife alone before radiotherapy developed RN during follow-up. Surgical resection for the cerebral RN was performed in nine patients, and the other three patients received medical treatment. The clinical features, magnetic resonance imaging (MRI), surgical findings, and pathological sections are reviewed. The diagnosis of RN was confirmed by histological study in all the patients; those with surgical and medical treatment recovered. As a major complication of radiotherapy, from the clinical and neuroradiological points of view, RN may simulate tumor recurrence. Due to the increasing number of patients with RN who will need to be treated in future years, the definite diagnosis and appropriate treatment of RN remain critical.

Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis

PurposeMany patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN). Methods and materialsAll patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests. ResultsOf 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk (P = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus ≥30 Gy revealed no effect of dose on RN rate. Additionally, among patients who received multiple SRS treatments, number of treated lesions was not predictive of RN incidence. ConclusionOur results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

Management Approach for Recurrent Brain Metastases Following Upfront Radiosurgery May Affect Risk of Subsequent Radiation Necrosis

Purpose Many patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN). Methods and materials All patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests. Results Of 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk (P = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus ≥30 Gy revealed no effect of dose on RN rate. Additionally, among patients who received multiple SRS treatments, number of treated lesions was not predictive of RN incidence. Conclusion Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

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.

Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain.

New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

AT-41MULTI-CENTER CLINICAL TRIAL OF INTRAVENOUS ADMINISTRATION OF BEVACIZUMAB FOR THE TREATMENT OF RADIATION NECROSIS IN THE BRAIN TO OBTAIN NDA APPLICATION FOR ON LABEL USE IN JAPAN

Recent radiotherapeutic modalities including particle radiotherapy, IMRT, and SRS are able to irradiate tumor tissue with high absorbed doses. These radiation therapies are promising to provide a longer survival in patients with CNS malignant tumors, compared to conventional X-ray radiotherapy. Simultaneously radiation necrosis (RN) has been a serious problem in such patients. However, there is no effective treatment for progressive RN so far. VEGF has been reported to play an important role in the progression of RN. Some clinical reports including ours demonstrate good results of bevacizumab treatment for RN. However, so far, no country gives a permission to use bevacizumab for symptomatic radiation necrosisin the brain as on label use. We initiated a nation-wide multicenter clinical trial in Japan, with the correct diagnosis of RN by amino-acid PET, to obtain a new drug approval (NDA) applications from Japanese FDA, based on public knowledge. Primary endpoint was the improvement of cerebral edema in periodic MRI. Secondary endpoint were safety, reduction of steroids, improvement of KPS and recurrence rate of RN within a year. The back ground of the patients are as follows; primary brain tumors such as GBM, metastatic brain tumors and head and neck cancers are 28 cases (68.3%), 12 cases (29.3%) and 1 case (2.4%), respectively. Applied radiation modalities are as follows; external beam radio-therapy 17 cases, SES 29 cases, hypo-fractionated IMRT 4 cases, proton beam particle radiation 3 cases and boron neutron capture therapy 1 case. Totally 41 cases of patients' enrollment finished. Last patient, last visit was in April 2014. The results are now opening and hopefully we can present them in SNO meeting.

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.

Anti-VEGF antibodies mitigate the development of radiation necrosis in mouse brain.

To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model. Cohorts of mice were irradiated with single-fraction 50- or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology. Hematoxylin and eosin-stained sections of brains from irradiated, non-Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1-treated and non-Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain. The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis.

The roles of platelet-derived growth factors and their receptors in brain radiation necrosis

BackgroundBrain radiation necrosis (RN) occurring after radiotherapy is a serious complication. We and others have performed several treatments for RN, using anticoagulants, corticosteroids, surgical resection and bevacizumab. However, the mechanisms underlying RN have not yet been completely elucidated. For more than a decade, platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been extensively studied in many biological processes. These proteins influence a wide range of biological responses and participate in many normal and pathological conditions. In this study, we demonstrated that PDGF isoforms (PDGF-A, B, C, and D) and PDGFRs (PDGFR-α and β) are involved in the pathogenesis of human brain RN. We speculated on their roles, with a focus on their potential involvement in angiogenesis and inflammation in RN.MethodsSeven surgical specimens of RN, obtained from 2006 to 2013 at our department, were subjected to histopathological analyses and stained with hematoxylin and eosin. We qualitatively analyzed the protein expression of each isoform of PDGF by immunohistochemistry. We also examined their expression with double immunofluorescence.ResultsAll PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB). PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN. PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.ConclusionsPDGFs/PDGFRs play critical roles in angiogenesis and possibly in inflammation, and they contribute to the pathogenesis of RN, irrespective of the original tumor pathology and applied radiation modality. Treatments for the inhibition of PDGF-C, PDGF-D, and PDGFR-α may provide new approaches for the treatment of RN induced by common radiation therapies.

An analysis of radiation necrosis of the central nervous system treated with bevacizumab

Radiation necrosis is a devastating complication following radiation to the central nervous system. The purpose of this study was to perform a comprehensive analysis of cases in the literature using bevacizumab, a monoclonal antibody against vascular endothelial growth factor, as treatment for radiation necrosis. A MEDLINE/PubMed search of articles about the use of bevacizumab for radionecrosis treatment yielded 16 studies published between 2007 and 2012. Data was summarized according to patient characteristics, treatment received and outcomes measured. A total of 71 unique cases were identified that met the inclusion criteria. The median age at the time of treatment with bevacizumab was 47years. The most common tumors treated were glioblastoma (31%), anaplastic glioma (14%), and metastatic brain tumors (15%). The median time from ending radiotherapy to starting treatment with bevacizumab was 11months and the median follow up time after bevacizumab treatment was 8months. The median number of cycles of bevacizumab was administered was 4, and the median dosage of bevacizumab was 7.5mg/kg. The median time elapsed between cycles of bevacizumab was 2weeks. Overall, pre and post treatment imaging revealed a median decrease in T1 contrast enhancement of 63%, and a 59% median decrease in T2/FLAIR signal abnormality. Treatment with bevacizumab resulted in a significant radiographic response for patients with radionecrosis. The median dosage of bevacizumab of 7.5mg/kg for four cycles every 2weeks should be considered as a treatment option in this patient population.

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.

Results of a questionnaire regarding practice patterns for the diagnosis and treatment of intracranial radiation necrosis after SRS

Although stereotactic radiosurgery (SRS) is an effective treatment option for patients with brain tumors, its increased use has raised concern for increased incidence of radiation necrosis (RN). No established standard or guidelines exists regarding non-invasive techniques to diagnose or treat RN. This study was conducted to assess current patterns of evaluation and treatment of RN among physicians who treat intracranial malignancies. A questionnaire consisting of 20 questions was sent to 3,041 members of the American Society for Radiation Oncology (ASTRO) and the Society for Neurologic Oncology (SNO). Questions addressed demographics, utilization of SRS, perceptions regarding RN diagnosis treatment, approach to steroid-refractory RN, and management of two clinical scenarios using Kwiksurvey© software. The survey response rate was 8.74 % (266/3,041). Most respondents practice in an academic and/or university setting (62 %) at a facility that performs SRS (94 %) with a variety of systems. The number of annual cases performed at the participant's institution varied from <50 to >400, with a wide degree of variability. Most respondents practice at an institution that performs 50-100 cases/year (28 %). The most common range of symptomatic RN seen in clinical practice was 1-5 % (61 %). Most respondents reported that asymptomatic RN occurs in 6-10 % (33 %). Favored non-invasive diagnostic mechanisms were clinical evaluation (37 %) and MRI (19 %). In response to a clinical scenario depicting an asymptomatic patient post-SRS for brain metastasis with an enlarging lesion and edema at the treatment site, most respondents felt the image represented RN or a combination of RN and tumor progression. Most (58 %) favored short-term follow-up with repeat MRI. Ninety-three percent of the respondents initiated steroids as a first-line approach if patient was to develop symptoms. Steroids were the preferred first therapy in symptomatic patients on initial follow-up (81 %). In steroid-refractory patients, most recommend surgical intervention (63 %). Most physicians who responded to this questionnaire believe that post-SRS RN is uncommon (≤10 % of cases). The approach to establish the diagnosis of RN is variable. Steroids are the most commonly utilized first-line treatment for suspected RN. Considerable variation exists in the management of steroid-refractory RN. Additional studies are required to establish guidelines for evaluation and treatment of RN.

Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery

Cerebral radiation necrosis (RN) is a difficult to treat complication of stereotactic radiosurgery (SRS) that can result in progressive neurologic decline. Currently, steroids are the standard of care treatment for brain RN despite their adverse effect profile and limited efficacy. The purpose of this study was to evaluate the treatment efficacy of cerebral RN to bevacizumab in patients with brain metastases previously treated with SRS. We retrospectively reviewed 14 lesions in 11 patients treated with bevacizumab for brain RN secondary to SRS for their brain metastases. Steroid dosing, RN-associated symptoms, and magnetic resonance imaging (MRI) scans were examined before, during, and after bevacizumab administration. Of the 11 patients included, 6 had metastatic non-small cell lung cancer, and 5 had metastatic breast cancer. The mean percentage decrease in RN volume seen on T1 post-Gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI at first follow-up, at a mean of 26 days (range, 15-43 days), was 64.4% and 64.3%, respectively. MRI changes were sustained on follow-up MRI scans, obtained at a mean of 33 days (range, 7-58 days) after bevacizumab discontinuation. After bevacizumab treatment, all patients initially receiving steroids had a reduction in steroid requirement, and all but one had an improvement in or stability of RN-associated symptoms. No patients experienced intratumoral bleeds or other adverse effects related to their bevacizumab treatment. Bevacizumab is effective and safe for the treatment of RN after SRS for brain metastasis. In this context, bevacizumab offers symptomatic relief, a reduction in steroid requirement, and a dramatic radiographic response.

Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

脳放射線壊死の成因と治療 : 高度医療(第3項先進医療)の申請

脳放射線壊死の成因と治療 : 高度医療(第3項先進医療)の申請

Treatment of steroid refractory, Gamma Knife related radiation necrosis with bevacizumab: Case report and review of the literature

Radiation necrosis is the most significant complication associted with Gamma Knife radiosurgery. It typically becomes manifest s a necrotic white matter lesion 3 or more months following treatent [3]. Treatment volume and radiation dose are the two most mportant predictors of radiation necrosis. Once radiation necrois has become clinically apparent treatment has historically been imited to corticosteroids. Antiplatelet agents, anticoagulants and yperbaric oxygen have been studied but there is currently minimal igh quality evidence to support their use in routine clinical pracice [6]. If the radiation necrosis fails to respond to steroid treatment herapeutic options are limited. Recent trials have highlighted a potential role for bevacizumab, a onoclonal antibody directed against vascular endothelial growth actor (VEGF) in the treatment of radiation necrosis from convenional radiation therapy [14]. We present a case of symptomatic adiation necrosis following Gamma Knife radiosurgery for muliple atypical WHO grade II meningiomas initially unresponsive o steroid treatment and ultimately responsive to bevacizumab herapy.