{"product_id":"bevacizumab-avastin-for-childhood-brain-and-spinal-cord-tumors-a-comprehensive-review","title":"Bevacizumab (Avastin) for Childhood Brain and Spinal Cord Tumors: A Comprehensive Review","description":"\u003cp\u003eThis comprehensive review examines how bevacizumab (Avastin), a drug that blocks new blood vessel formation, is used to treat brain and spinal cord tumors in children. The authors analyzed studies across multiple tumor types. The authors found the strongest benefits in recurrent medulloblastoma when combined with two chemotherapy drugs. The authors found the strongest benefits in optic pathway glioma for preserving vision. The authors found the strongest benefits in reducing steroid dependence for radiation necrosis. Results were disappointing for newly diagnosed high-grade gliomas and diffuse intrinsic pontine glioma. The drug was generally well tolerated, with side effects like high blood pressure and nosebleeds that were manageable with monitoring.\u003c\/p\u003e\n\n\u003ch1\u003eBevacizumab (Avastin) for Childhood Brain and Spinal Cord Tumors: A Comprehensive Review\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n\u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#how-it-works\"\u003eHow Bevacizumab Works\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#low-grade-glioma\"\u003eBevacizumab for Pediatric Low-Grade Glioma\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#visual-benefit\"\u003eVision Benefits in Optic Pathway Glioma\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#high-grade-glioma\"\u003eBevacizumab for High-Grade Glioma\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#dipg\"\u003eBevacizumab for Diffuse Intrinsic Pontine Glioma\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#other-tumors\"\u003eBevacizumab for Other Central Nervous System Tumors\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#radiation-necrosis\"\u003eBevacizumab for Radiation Necrosis\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#cerebral-edema\"\u003eBevacizumab for Cerebral Edema\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#side-effects\"\u003eSide Effects and Safety\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Research\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#future-directions\"\u003eFuture Directions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eBevacizumab is not FDA-approved for pediatric brain tumors but is used off-label; evidence comes from many small, often retrospective studies.\u003c\/li\u003e\n\u003cli\u003eIn a phase II trial, adding bevacizumab to temozolomide and irinotecan for recurrent medulloblastoma improved median overall survival from 13 to 19 months.\u003c\/li\u003e\n\u003cli\u003eBevacizumab-based therapy improved vision in some children with optic pathway glioma; one study of 31 patients achieved ophthalmologic disease control in 88%.\u003c\/li\u003e\n\u003cli\u003eThe HERBY trial of 121 patients found no survival benefit from adding bevacizumab for newly diagnosed high-grade glioma, with more serious adverse events.\u003c\/li\u003e\n\u003cli\u003eCommon side effects include hypertension, proteinuria, and nosebleeds, usually manageable; about 1 in 10 children in one review had grade 3 or higher toxicity.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eBrain and other nervous system tumors are the most common type of solid tumors in children. They are the second most common form of childhood cancer after leukemia. Treatment options for children with these tumors are often limited, and researchers continue to search for better therapies.\u003c\/p\u003e\n\n\u003cp\u003ePediatric brain tumors are highly diverse. Each tumor type requires specific molecular characterization and treatment approaches. The World Health Organization's Central Nervous System classification (known as CNS5) represents the most current understanding of the biology behind these tumors.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab is often used off-label in pediatric neuro-oncology. This means the drug is not officially approved by regulatory agencies for these specific uses in children. The evidence for using bevacizumab in children with brain tumors is often fragmented across many small studies. This review aims to provide an organized summary of how well the drug works across different tumor types.\u003c\/p\u003e\n\n\u003cp\u003eThe authors also identified gaps in the medical literature to guide future research. They examined outcomes including overall survival, event-free survival, progression-free survival, vision and hearing improvements, steroid use, quality of life, and toxicity.\u003c\/p\u003e\n\n\u003ch2 id=\"how-it-works\"\u003eHow Bevacizumab Works\u003c\/h2\u003e\n\n\u003cp\u003eBlood vessel formation has long been considered a hallmark of cancer. However, some tumors can grow without forming new blood vessels. Bevacizumab (brand name Avastin) is a monoclonal antibody. A monoclonal antibody is a laboratory-made protein that targets a specific molecule in the body.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab selectively binds to Vascular Endothelial Growth Factor (VEGF). VEGF is a protein that drives the formation of new blood vessels. By binding to VEGF, bevacizumab inhibits the pathways that drive new blood vessel formation. This inhibition reduces blood supply to tumor tissues.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab was first approved by the Food and Drug Administration (FDA) in 2004 for treating metastatic colorectal cancer. Since then, it has been approved for several solid tumors in both children and adults.\u003c\/p\u003e\n\n\u003cp\u003eThe drug was first introduced in pediatric settings in 2008. A study evaluated bevacizumab in pediatric patients with recurrent or progressive solid tumors. Among patients who showed partial response, two had astrocytoma grade III. The authors concluded that the treatment had a satisfactory acute safety profile and showed promising antitumor activity.\u003c\/p\u003e\n\n\u003cp\u003eDespite the evidence presented in this review, bevacizumab is currently not FDA-approved for managing pediatric brain tumors.\u003c\/p\u003e\n\n\u003ch2 id=\"low-grade-glioma\"\u003eBevacizumab for Pediatric Low-Grade Glioma\u003c\/h2\u003e\n\n\u003cp\u003ePediatric low-grade glioma (pLGG) is the most common form of central nervous system tumor in children. It accounts for more than 30% of all central nervous system tumors in this population. The World Health Organization's fifth edition classification separates pLGG into three families: pediatric type diffuse low-grade gliomas, circumscribed astrocytic gliomas, and glioneural and neuronal tumors.\u003c\/p\u003e\n\n\u003cp\u003eLow-grade gliomas are slow-growing and heterogeneous tumors. The standard of care involves surgical resection, which remains the gold standard when feasible. When surgical resection is not possible or is incomplete, chemotherapy and rarely radiotherapy can be considered. Radiation therapy is generally not favored due to its adverse effects on the growing brain and risk of significant long-term morbidities.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eKey Study Results for Low-Grade Glioma:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003ePacker and colleagues conducted a retrospective review of ten pediatric patients with multiple recurrent pLGG. The combination of bevacizumab and irinotecan led to objective radiographic responses in seven patients (78%, with one patient deemed non-evaluable). Clinical improvement occurred in seven patients (78%), including weight gain, improvements in visual acuity, reversal of psychomotor retardation, and improvement in developmental status.\u003c\/li\u003e\n\u003cli\u003eThe Pediatric Brain Tumor Consortium initiated a study (PBTC-022) evaluating bevacizumab and irinotecan in 35 patients with recurrent low-grade gliomas. The median age was 8.4 years. Only two patients experienced sustained partial response, with an objective response rate of 6%. All but one patient experienced disease progression at a median of 5 months following treatment cessation.\u003c\/li\u003e\n\u003cli\u003eA nationwide evaluation in the United Kingdom found that partial response occurred in 40% of patients, stable disease in 49%, and progressive disease in 11%. The median time to best response was 3 months. Disease progression was seen in 65% of patients at a median of 8 months after stopping treatment. Notably, 85% of patients received bevacizumab-based therapy as third-line treatment and still experienced benefit.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBevacizumab is generally tolerated in pediatric patients with low-grade gliomas. Most studies report grade 1 or 2 toxicities, including hypertension and fatigue, which are usually reversible. However, a systematic review by Lu and colleagues reported that an estimated 1 in 10 children experienced grade 3 toxicity or higher.\u003c\/p\u003e\n\n\u003cp\u003eAs an antiangiogenic agent, bevacizumab rapidly changes the permeability of the blood-brain barrier. The MRI response to bevacizumab may be overstated based on Response Assessment in Neuro-Oncology criteria that use T1 contrast sequences. This may explain why the real benefit of bevacizumab in terms of response rate has been questioned.\u003c\/p\u003e\n\n\u003cp\u003eLevenbaum and colleagues highlighted the lack of data on the effects of bevacizumab on cystic components of pLGG. These cysts may enlarge and cause clinical complications. They presented a case series of four patients with predominantly cystic LGG. All patients demonstrated a response to bevacizumab with reduced cyst size.\u003c\/p\u003e\n\n\u003ch2 id=\"visual-benefit\"\u003eVision Benefits in Optic Pathway Glioma\u003c\/h2\u003e\n\n\u003cp\u003eStandard chemotherapy regimens have been shown to produce minimal visual improvements in patients with optic pathway glioma (OPG), whether related to neurofibromatosis type 1 (NF1) or sporadic. The use of bevacizumab-based therapy has demonstrated visual improvements in patients with OPG and associated vision loss.\u003c\/p\u003e\n\n\u003cp\u003eA 2013 case series from Avery and colleagues reported on four pediatric patients with OPG who received bevacizumab following progressive worsening in visual acuity and visual field assessments. Three patients had previously received chemotherapy including carboplatin and vincristine. All patients demonstrated significant improvements in visual acuity, visual field, or both. One patient demonstrated complete recovery of visual field deficits, while another demonstrated complete recovery of visual acuity. Three patients with visual acuity loss experienced improvement ranging from 0.3 logMAR (moderate) to 0.8 logMAR (significant).\u003c\/p\u003e\n\n\u003cp\u003eHwang and colleagues studied 14 patients and noted that six children had cancer-related visual impairment. With initial bevacizumab-based therapy, 4 of 6 patients (67%) demonstrated visual improvement. One patient demonstrated recurrent visual improvement with each course of treatment.\u003c\/p\u003e\n\n\u003cp\u003ePacker and colleagues reported improvement in visual acuity in 2 of 9 evaluable patients (22%) receiving combination treatment with bevacizumab and irinotecan for recurrent low-grade gliomas.\u003c\/p\u003e\n\n\u003cp\u003eA recent single-institution retrospective study evaluated bevacizumab as second-line treatment for pediatric patients with unresectable pLGG. The median age at treatment initiation was 8.1 years. All patients showed no signs of further disease progression at the 3-month mark. Approximately one-third of patients showed radiological and visual improvement, while two-thirds had stable disease. Among patients with visual impairment but radiological stability at the end of treatment, 71% had an NF1 diagnosis. Progression-free survival was 91.4% at 12 months but reduced to 31.4% at 36 months.\u003c\/p\u003e\n\n\u003cp\u003eIn a study evaluating bevacizumab as a single-agent treatment for OPG in 31 patients under 19 years of age, ophthalmologic disease control was achieved in 88% of patients.\u003c\/p\u003e\n\n\u003cp\u003eIn a nationwide multi-institutional study conducted in the Netherlands, pediatric patients with OPG who received bevacizumab demonstrated favorable short-term outcomes. Most patients experienced temporary stabilization in tumor volume and improvement in visual function. Interestingly, 64% of patients experienced radiological tumor progression after a median of 20 months since initiating therapy. However, 74.4% of eyes evaluated had stable visual acuity, and 73% of visual fields improved. This finding is consistent with the known poor correlation between radiological and clinical findings in pediatric patients with OPG. Among patients in this cohort, those with KIAA1549-BRAF fusion had a lower progression-free survival compared to those with NF1-OPG.\u003c\/p\u003e\n\n\u003cp\u003eThe final results of OZM-063, a clinical trial examining combination vinblastine and bevacizumab compared to vinblastine alone in children with unresectable or progressive LGG, are awaited. In this trial, response rate at 6 months is the primary outcome measure. Progression-free survival, 5-year overall survival, and visual improvement are among the secondary outcome measures. Preliminary results suggest that adding bevacizumab to vinblastine could result in a better radiological response and potential visual benefit.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab has often been used as a second-line treatment or later. However, data from the OZM-063 study and the United Kingdom study by Green and colleagues suggest that using bevacizumab at an earlier stage may prove more beneficial. Using bevacizumab at an earlier stage may prove particularly beneficial for patients with impaired vision.\u003c\/p\u003e\n\n\u003ch2 id=\"high-grade-glioma\"\u003eBevacizumab for High-Grade Glioma\u003c\/h2\u003e\n\n\u003cp\u003ePediatric High-Grade Gliomas (pHGGs) are aggressive brain tumors that account for 8-12% of central nervous system tumors in children. Despite advancements in treatment, the 5-year survival rate remains below 20%. The standard of care involves maximal safe surgical resection followed by radiotherapy and usually adjuvant chemotherapy.\u003c\/p\u003e\n\n\u003cp\u003eWhile bevacizumab has demonstrated promising results in adults with recurrent high-grade gliomas, its use in pediatric high-grade gliomas has demonstrated less satisfactory results.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eKey Study Results for High-Grade Glioma:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003eThe Pediatric Brain Tumor Consortium led a phase II study evaluating bevacizumab and irinotecan in pediatric patients with recurrent central nervous system tumors. These tumors included high-grade glioma and diffuse intrinsic pontine glioma. The median age was 15 years. The combination treatment did not result in sustained objective responses.\u003c\/li\u003e\n\u003cli\u003eThe HERBY trial was a phase II, open-label, multicenter study. The HERBY trial assessed whether adding bevacizumab to standard radiotherapy plus temozolomide would improve outcomes in pediatric patients with newly diagnosed non-brainstem high-grade glioma. The trial enrolled 121 patients and found no significant improvement in event-free survival or overall survival with the addition of bevacizumab. Bevacizumab was associated with a higher rate of serious adverse events and treatment discontinuations. In a post-hoc analysis, Mackay and colleagues found that tumors with MAPK pathway alterations demonstrated improved survival when treated with bevacizumab.\u003c\/li\u003e\n\u003cli\u003eThe Children's Oncology Group reported results of a randomized phase II multi-center study (ACNS0822). The study evaluated concurrent vorinostat or bevacizumab with focal radiation therapy compared to standard concurrent temozolomide with focal radiation therapy. Among 90 randomized patients, 1-year event-free survival rates were 43.8% for the bevacizumab arm, 41.4% for the vorinostat arm, and 59.3% for the temozolomide arm. There were no statistically significant differences between arms.\u003c\/li\u003e\n\u003cli\u003eNarayana and colleagues conducted a study evaluating bevacizumab in pediatric patients with recurrent high-grade glioma. The results were disappointing and notably lower than those observed in adult series. The radiographic response rate was 16.7%. The median progression-free survival was 2.5 months. The overall survival was 5.5 months.\u003c\/li\u003e\n\u003cli\u003eDetti and colleagues showed that bevacizumab could play a role in improving survival based on their retrospective single-center analysis of 92 patients with recurrent high-grade glioma.\u003c\/li\u003e\n\u003cli\u003eA scoping review from Fu and colleagues suggested that bevacizumab seems to improve progression-free survival and quality of life in patients with recurrent glioblastoma.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe varied results seen between adult and pediatric high-grade glioma with respect to VEGF inhibition could suggest that angiogenesis in pediatric high-grade glioma is regulated by multiple growth factors. These include platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF).\u003c\/p\u003e\n\n\u003cp\u003eAt Seattle Children's Hospital, Crotty and colleagues retrospectively studied 36 children with pediatric high-grade glioma and diffuse intrinsic pontine glioma treated with radiotherapy followed by maintenance temozolomide, irinotecan, and bevacizumab. Survival in pediatric high-grade glioma was comparable to results obtained using other contemporary three-drug treatment protocols. In diffuse intrinsic pontine glioma, 1-year overall survival appeared higher than when using the historical regimen of temozolomide alone. Despite these results, in pediatric high-grade glioma, a cure was rarely observed, and in diffuse intrinsic pontine glioma, it was non-existent.\u003c\/p\u003e\n\n\u003ch2 id=\"dipg\"\u003eBevacizumab for Diffuse Intrinsic Pontine Glioma\u003c\/h2\u003e\n\n\u003cp\u003eThe median survival time of patients with diffuse intrinsic pontine glioma (DIPG) has remained unchanged for decades. Focal radiotherapy is the only effective palliative treatment. The introduction of re-irradiation has contributed to extending the survival of some patients, but the overall 5-year survival of this condition remains below 5%.\u003c\/p\u003e\n\n\u003cp\u003eWith other types of tumors demonstrating VEGF overexpression, bevacizumab appeared to be a potential therapeutic option.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eKey Study Results for DIPG:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003eThe Pediatric Brain Tumor Consortium began a phase II trial in children with malignant glioma and DIPG. Bevacizumab and irinotecan were administered to 31 eligible patients, 17 of whom had DIPG. No sustained responses were observed in any of the patients. The median progression-free survival was only 2.3 months, and at 6 months, only 9.7% demonstrated progression-free survival.\u003c\/li\u003e\n\u003cli\u003eIn 2021, El-Khouly and colleagues reported a phase I\/II study with erlotinib paired with bevacizumab and irinotecan. They reported an overall survival of 13.8 months. This result was similar to that obtained in the Seattle Children's Hospital study but longer than the 10 months achieved with radiotherapy alone. The treatment regimen was especially effective in patients stratified as intermediate or high risk (12.8 months and 18.7 months, versus 9.7 and 7.0 months).\u003c\/li\u003e\n\u003cli\u003eThe Seattle Children's Hospital conducted a retrospective study evaluating this regimen in pediatric patients with Grade III or IV high-grade glioma or DIPG. This regimen was found to be tolerable and showed a slight improvement in survival for DIPG patients compared to temozolomide alone. The 1-year survival rate was 80% compared to 45.3% based on International DIPG registry data and 40% seen in patients treated with temozolomide alone in the ACNS0126 trial. However, survival for DIPG patients treated with this regimen decreased to 10% at the 2-year mark and to 0% at 5 years.\u003c\/li\u003e\n\u003cli\u003eIn a systematic review on the role of bevacizumab-based regimens in the treatment of DIPG, Evans and colleagues found conflicting conclusions among included papers. These papers examined median overall survival, radiological response, symptom improvement, quality of life, steroid use, and radiation necrosis. The findings may suggest that the use of bevacizumab could result in an improvement in quality of life. The findings may also suggest that the use of bevacizumab could result in reduced steroid use. However, the authors concluded that the evidence is not strong enough to generalize the results.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"other-tumors\"\u003eBevacizumab for Other Central Nervous System Tumors\u003c\/h2\u003e\n\n\u003cp\u003eBevacizumab has also shown promise in other central nervous system tumors, such as schwannomas, in the setting of neurofibromatosis type 2 (NF2).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSchwannoma Results:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cp\u003eIn a systematic review by Tops and colleagues, the authors demonstrated that bevacizumab's benefit on tumor volume in children is less pronounced than in adults. Tumor regression occurred in 11% of pediatric patients, size stability in 68%, and tumor progression in 9-22%. In contrast, in adults undergoing bevacizumab-based treatment, tumor regression was observed in 30% of patients in a meta-analysis by Shi and colleagues. Tumor regression was observed in 38% of patients in a systematic review by Chiranth and colleagues. Chiranth and colleagues also found tumor progression in only 9% of patients.\u003c\/p\u003e\n\n\u003cp\u003eHowever, the effect of bevacizumab on hearing function is more comparable to adults' results. Improved hearing occurred in 33% of patients, worsened hearing in 7%, and hearing remained stable in 60%. Renzi and colleagues demonstrated that 61% of patients with initial hearing loss demonstrated improved hearing after six months of bevacizumab. Thus, bevacizumab seems to be a promising option for NF2 in children, especially with regard to hearing preservation.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEpendymoma Results:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cp\u003eGururangan and colleagues conducted the first efficacy study of bevacizumab in the treatment of recurrent ependymoma. Thirteen evaluable patients were administered bevacizumab and irinotecan for a median of three courses. No objective response was observed, nor was there an improvement in the rate of disease stabilization compared to standard regimens. The reason for this lack of response was not clear to the authors. They speculate that it may be due to biologic heterogeneity of ependymomas or implication of angiogenesis factors other than VEGF.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eMedulloblastoma Results:\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cp\u003eThe first report on the use of bevacizumab in medulloblastoma was in 2011. Aguilera and colleagues described two patients with recurrent medulloblastoma treated with a combination of bevacizumab, irinotecan with or without temozolomide who experienced sustained tumor progression.\u003c\/p\u003e\n\n\u003cp\u003eSubsequently, in a phase II trial, Levy and colleagues compared the combination of temozolomide-irinotecan versus temozolomide, irinotecan, and bevacizumab in recurrent medulloblastoma or supratentorial primitive neuroectodermal tumor. Supratentorial primitive neuroectodermal tumor is an older term currently replaced by new classifications. They reported an improved median overall survival (13 months vs. 19 months) and median event-free survival (6 months vs. 9 months) with the use of bevacizumab. The results of this trial have influenced clinical practice. The combination of irinotecan, temozolomide, and bevacizumab has now become a standard of care for patients with recurrent medulloblastoma in many institutions.\u003c\/p\u003e\n\n\u003cp\u003eUnfortunately, this study was designed before the awareness of medulloblastoma subgrouping. Whether the benefit of bevacizumab is subgroup-specific was unknown. Importantly, this study did not show any advantage of bevacizumab in non-medulloblastoma (spNET) patients.\u003c\/p\u003e\n\n\u003cp\u003eThe Seattle Children's Hospital followed the protocol in the above study, concluding that their outcomes were similar to those published in clinical trials. They add that this treatment regimen would be especially useful in patients geographically limited from care.\u003c\/p\u003e\n\n\u003cp\u003eAn ongoing clinical trial is combining the triple therapy of temozolomide, irinotecan, and bevacizumab with cRIT 131I-omburtamab in recurrent medulloblastoma. The latter is a medication consisting of the delivery of radiolabeled tumor-specific antibodies.\u003c\/p\u003e\n\n\u003cp\u003eFinally, the Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial (MEMMAT) evaluated a multi-drug regimen for the treatment of recurrent medulloblastoma. The treatment combined daily oral thalidomide, fenofibrate, celecoxib, and 21-day cycles of either oral etoposide or cyclophosphamide in a metronomic fashion. The protocol also included intravenous bevacizumab and intraventricular therapy (etoposide and cytarabine). This unique approach aims to target the tumor microenvironment both by targeting angiogenesis directly and by activating the immune system. The trial yielded promising results, with 23 of 40 patients (57.5%) achieving disease control following six months of treatment. Of the 23 patients, three (7.5%) had no evidence of disease, six (15%) had a complete response, nine (22.5%) had a partial response, and five (12.5%) demonstrated stable disease. Unfortunately, 17 patients had to cease treatment due to disease progression.\u003c\/p\u003e\n\n\u003ch2 id=\"radiation-necrosis\"\u003eBevacizumab for Radiation Necrosis\u003c\/h2\u003e\n\n\u003cp\u003eRadiotherapy is a central part of the treatment plan for many pediatric brain tumors. Despite its benefit, it may be associated with substantial side effects, including a risk of radiation necrosis. Radiation necrosis is the death of healthy brain tissue caused by radiation treatment.\u003c\/p\u003e\n\n\u003cp\u003eThe pathophysiology behind radiation necrosis is still unclear. Vellayappan and colleagues suggest that it involves endothelial injury and subsequent vascular changes in both healthy and tumor tissue. Among the enumerated inflammatory markers involved in this process are VEGF, TNF-alpha, and HIF1.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab has shown benefit in diminishing steroid use in radiation necrosis. The greatest benefits were observed in cases such as diminished steroid use in radiation necrosis.\u003c\/p\u003e\n\n\u003ch2 id=\"cerebral-edema\"\u003eBevacizumab for Cerebral Edema\u003c\/h2\u003e\n\n\u003cp\u003eCerebral edema is swelling in the brain that can occur with brain tumors. Bevacizumab has been used to treat cerebral edema in pediatric neuro-oncology patients. The drug's effect on blood vessel permeability may help reduce this swelling.\u003c\/p\u003e\n\n\u003ch2 id=\"side-effects\"\u003eSide Effects and Safety\u003c\/h2\u003e\n\n\u003cp\u003eThe medication was overall well tolerated in pediatric patients. Common adverse events include hypertension (high blood pressure), proteinuria (protein in the urine), and epistaxis (nosebleeds). These side effects were often manageable with surveillance and monitoring.\u003c\/p\u003e\n\n\u003cp\u003eIn pediatric patients with low-grade gliomas, the majority of studies reported grade 1 or 2 toxicities, including hypertension and fatigue, that are usually reversible. However, a systematic review from Lu and colleagues reported that an estimated 1 in 10 children experienced grade 3 toxicity or higher.\u003c\/p\u003e\n\n\u003cp\u003eIn the HERBY trial for high-grade glioma, bevacizumab was associated with a higher rate of serious adverse events and treatment discontinuations.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThe greatest benefits of bevacizumab were observed in specific situations:\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eRecurrent medulloblastoma:\u003c\/strong\u003e When combined with temozolomide and irinotecan, this combination has become a standard of care in many institutions. Median overall survival improved from 13 months to 19 months, and median event-free survival improved from 6 months to 9 months.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOptic pathway glioma:\u003c\/strong\u003e Bevacizumab has demonstrated visual improvements in patients with OPG and associated vision loss. Ophthalmologic disease control was achieved in 88% of patients in one study.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eRadiation necrosis:\u003c\/strong\u003e Bevacizumab has shown benefit in diminishing steroid use.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNeurofibromatosis type 2 with schwannomas:\u003c\/strong\u003e Bevacizumab shows promise for hearing preservation, with improved hearing in 33% of patients and stable hearing in 60%.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eResults were poorer in cases of newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas. The HERBY trial found no significant improvement in event-free survival or overall survival with the addition of bevacizumab for newly diagnosed high-grade glioma.\u003c\/p\u003e\n\n\u003cp\u003eIn consideration of the results, bevacizumab should be considered based on the tumor profile. Its outcome should be measured along functional endpoints, besides radiological evolution. This means that doctors should assess how patients feel and function, not just what scans show.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Research\u003c\/h2\u003e\n\n\u003cp\u003eThe evidence for using bevacizumab in pediatric neuro-oncology is often fragmented. Many studies are retrospective, meaning they look back at patient records rather than testing treatments in controlled experiments.\u003c\/p\u003e\n\n\u003cp\u003eSome studies were designed before awareness of tumor subgrouping. Whether the benefit of bevacizumab is subgroup-specific remains unknown for some tumor types.\u003c\/p\u003e\n\n\u003cp\u003eThe MRI response to bevacizumab may be overstated based on Response Assessment in Neuro-Oncology criteria. This is because bevacizumab rapidly changes the permeability of the blood-brain barrier. This may explain why the real benefit of bevacizumab in terms of response rate has been questioned.\u003c\/p\u003e\n\n\u003cp\u003eThere is a lack of data on the effects of bevacizumab on cystic components of pediatric low-grade glioma. These cysts may enlarge and cause clinical complications.\u003c\/p\u003e\n\n\u003cp\u003eIn a systematic review on the role of bevacizumab-based regimens in the treatment of DIPG, Evans and colleagues found conflicting conclusions among included papers. The authors concluded that the evidence is not strong enough to generalize the results.\u003c\/p\u003e\n\n\u003ch2 id=\"future-directions\"\u003eFuture Directions\u003c\/h2\u003e\n\n\u003cp\u003eContinued investigations into outcome measures will contribute to improving outcomes in this vulnerable population. Combination with targeted treatments and optimizing therapy are also important areas for future research.\u003c\/p\u003e\n\n\u003cp\u003eThe final results of OZM-063, a clinical trial examining combination vinblastine and bevacizumab compared to vinblastine alone in children with unresectable or progressive LGG, are awaited. Preliminary results suggest that adding bevacizumab to vinblastine could result in a better radiological response and potential visual benefit.\u003c\/p\u003e\n\n\u003cp\u003eAn ongoing clinical trial is combining the triple therapy of temozolomide, irinotecan, and bevacizumab with cRIT 131I-omburtamab in recurrent medulloblastoma.\u003c\/p\u003e\n\n\u003cp\u003eData from the OZM-063 study and the United Kingdom study by Green and colleagues suggest that using bevacizumab at an earlier stage may prove more beneficial. Using bevacizumab at an earlier stage may prove particularly beneficial for patients with impaired vision.\u003c\/p\u003e\n\n\u003cp\u003eMackay and colleagues found improved survival in pediatric high-grade glioma with MAPK pathway alterations. Given these findings, future research may focus on identifying which patients are most likely to benefit from bevacizumab.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is bevacizumab and how does it work?\u003c\/h3\u003e\n\u003cp\u003eBevacizumab, brand name Avastin, is a monoclonal antibody that selectively binds to Vascular Endothelial Growth Factor (VEGF), a protein that drives new blood vessel formation. By binding to VEGF, it inhibits pathways that drive new blood vessel formation, reducing blood supply to tumor tissues. It was first approved by the FDA in 2004 for metastatic colorectal cancer and was first introduced in pediatric settings in 2008.\u003c\/p\u003e\n\u003ch3\u003eIs bevacizumab approved for treating childhood brain tumors?\u003c\/h3\u003e\n\u003cp\u003eNo. Bevacizumab is currently not FDA-approved for managing pediatric brain tumors. It is often used off-label in pediatric neuro-oncology, meaning it is not officially approved by regulatory agencies for these specific uses in children. The evidence for its use in children with brain tumors is often fragmented across many small studies, and this review aims to organize that evidence.\u003c\/p\u003e\n\u003ch3\u003eWhat side effects might my child experience from bevacizumab?\u003c\/h3\u003e\n\u003cp\u003eThe medication was overall well tolerated in pediatric patients. Common adverse events include hypertension (high blood pressure), proteinuria (protein in the urine), and epistaxis (nosebleeds). These were often manageable with surveillance and monitoring. In pediatric low-grade gliomas, most studies reported grade 1 or 2 toxicities, including hypertension and fatigue, usually reversible. However, a systematic review estimated 1 in 10 children experienced grade 3 toxicity or higher.\u003c\/p\u003e\n\u003ch3\u003eHow well does bevacizumab work for recurrent medulloblastoma?\u003c\/h3\u003e\n\u003cp\u003eIn a phase II trial, adding bevacizumab to temozolomide and irinotecan for recurrent medulloblastoma improved median overall survival from 13 to 19 months and median event-free survival from 6 to 9 months. This combination has become a standard of care in many institutions. However, the study did not show any advantage in non-medulloblastoma patients, and it was designed before awareness of medulloblastoma subgrouping.\u003c\/p\u003e\n\u003ch3\u003eCan bevacizumab help preserve vision in optic pathway glioma?\u003c\/h3\u003e\n\u003cp\u003eYes, bevacizumab-based therapy has demonstrated visual improvements in patients with optic pathway glioma and associated vision loss. In one study of 31 patients under 19 years, ophthalmologic disease control was achieved in 88%. In a nationwide Netherlands study, 74.4% of evaluated eyes had stable visual acuity and 73% of visual fields improved. However, radiological tumor progression occurred in 64% after a median of 20 months.\u003c\/p\u003e\n\u003ch3\u003eWhat were the results for newly diagnosed high-grade glioma and DIPG?\u003c\/h3\u003e\n\u003cp\u003eResults were disappointing. The HERBY trial, enrolling 121 patients with newly diagnosed non-brainstem high-grade glioma, found no significant improvement in event-free or overall survival with added bevacizumab, and it was associated with more serious adverse events and treatment discontinuations. For diffuse intrinsic pontine glioma, a phase II trial observed no sustained responses, with median progression-free survival of only 2.3 months and 9.7% progression-free survival at 6 months.\u003c\/p\u003e\n\u003ch3\u003eWhen should a child with a brain or spinal cord tumor seek a second opinion about bevacizumab (Avastin) treatment?\u003c\/h3\u003e\n\u003cp\u003eA second opinion can help when the tumor type or treatment goal is unclear. Bevacizumab is used off-label in children and is not FDA-approved for pediatric brain tumors. Benefits differ by tumor: recurrent medulloblastoma combined with temozolomide and irinotecan improved median overall survival from 13 to 19 months, optic pathway glioma showed visual improvement, and radiation necrosis showed reduced steroid use. Results were poorer for newly diagnosed high-grade glioma and diffuse intrinsic pontine glioma. Because evidence is fragmented across small, often retrospective studies, an independent review of tumor profile and functional goals is reasonable. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal Article Title:\u003c\/strong\u003e Bevacizumab in Pediatric Neuro-Oncology.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e Current oncology (Toronto, Ont.)\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eLicense:\u003c\/strong\u003e CC BY (open access)\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Jacob Silverman, Sayanthen Sathyakumar, Hallie Coltin, Sebastien Perreault, Nada Jabado, Eric Bouffet, and Samuele Renzi\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e Current Oncology, 2025, Volume 32, Article 573\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e https:\/\/doi.org\/10.3390\/curroncol32100573\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication Dates:\u003c\/strong\u003e Received: 31 August 2025; Revised: 12 October 2025; Accepted: 14 October 2025; Published: 16 October 2025\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor Affiliations:\u003c\/strong\u003e McGill Faculty of Medicine and Health Sciences, Montréal, QC, Canada; Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Division of Hematology-Oncology, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada; Department of Neurology, Division of Child Neurology, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada; Department of Pediatrics, McGill University, Montreal, QC, Canada; The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Division of Pediatric Hematology-Oncology, Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, Division of Hematology-Oncology, CHU de Québec, Université Laval, Québec City, QC, Canada\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47807386845340,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/ddn-medical-article-bevacizumab-avastin-for-childhood-brain-and-spinal-cord-tumors-a-comprehensive-review-hero.png?v=1792819290","url":"https:\/\/diagnosticdetectives.com\/products\/bevacizumab-avastin-for-childhood-brain-and-spinal-cord-tumors-a-comprehensive-review","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}