Q&A on childhood brain tumors

The Q&A column on pediatric gliomas invites experts in the field of childhood brain tumors to address various questions regarding pediatric gliomas. Today we present the fourth issue, and we welcome your questions in the comments section!

1. Can low-grade gliomas be cured?  

Surgical resection is the primary treatment for low-grade gliomas and is generally safe and reliable. It can significantly improve overall survival rates and symptom control in children. Especially for those who undergo complete surgical resection, many children can achieve a cure, with a low chance of recurrence. Low-grade gliomas are benign tumors; as long as they are completely removed, they usually do not grow back, and there’s no need for subsequent radiotherapy or chemotherapy. For instance, pilocytic astrocytomas located in the cerebellar hemisphere with significant cystic changes have a high cure rate. As long as the tumor is safely and thoroughly removed, children can quickly return to normal learning and life without needing radiation or chemotherapy. Therefore, for low-grade gliomas located in the cerebral hemisphere, as long as the affected area is not extensive and doesn’t involve crucial functional regions, the chances of successful complete surgical resection and safety are guaranteed, leading to a good prognosis.

For low-grade gliomas that cause epilepsy, in addition to surgery, antiepileptic medications are needed for auxiliary control. After surgical resection, the child may only need to take antiepileptic medications for 1-2 years, and can stop if there are no seizures. The surgical and treatment outcomes for such low-grade gliomas are generally favorable.

However, low-grade gliomas located in deep and critical functional areas, such as optic pathway gliomas, cannot be completely removed, as doing so would affect the child's vision. In these cases, chemotherapy can be used to control the residual tumor, which may shrink or even disappear completely. For patients dissatisfied with chemotherapy results, radiation therapy can be considered. For low-grade gliomas in the densely packed areas of the thalamus and brainstem, if complete surgical resection is not possible, stereotactic biopsy followed by chemotherapy, or special radiation therapy such as Gamma Knife can be used to control tumor growth.

2. Which pediatric gliomas have better prognoses?  

Pediatric low-grade gliomas are the most common childhood brain tumors, accounting for 30% of all brain tumors. Overall, pediatric low-grade gliomas have a better prognosis than high-grade gliomas. Pediatric low-grade gliomas are divided into diffuse low-grade gliomas and localized low-grade gliomas. The prognosis of localized low-grade gliomas is generally better than that of diffuse low-grade gliomas.

Diffuse low-grade gliomas in children include diffuse astrocytomas with MYB or MYBL1 mutations; angiocentric gliomas with MYB; juvenile pilocytic astrocytomas; and diffuse low-grade gliomas with mutations in the MAPK signaling pathway. Localized low-grade gliomas, such as pilocytic astrocytomas, typically exhibit molecular characteristics such as KIAA1549-BRAF, BRAF, and NF1, and have the best prognosis. Among pediatric low-grade gliomas, pilocytic astrocytoma (PA) is the most common, often found in the posterior fossa, such as in the cerebellar hemisphere. After complete surgical resection, the 5-10 year survival rate exceeds 95%. The tumor location and the extent of resection are the two major factors that influence prognosis.

3. What are the treatment methods for low-grade gliomas?  

The treatment of pediatric low-grade gliomas (pLGG) includes surgery, chemotherapy, radiotherapy, and targeted drug therapy. There is currently a stronger emphasis on individualized treatment approaches that integrate multidisciplinary strategies, such as surgical intervention, radiation oncology, neuroimaging, neuropathology, and pediatric oncology. The surgical treatment of pediatric low-grade gliomas is complex and requires multidisciplinary participation to clarify the surgical objectives. Typically, these tumors are discovered incidentally or in the presence of seizures or headaches, but without obvious neurological deficits.

For pLGG, the best treatment method is the maximal safe surgical resection to achieve a cure, and this should always be considered. However, due to factors such as the tumor's location (such as in the hypothalamus and optic nerve pathway), the tumor's aggressiveness, or molecular subtype, complete resection may be difficult. Therefore, surgical goals may include total resection, partial resection for debulking, or biopsy (stereotactic puncture and endoscopic biopsy).

Radiotherapy is an effective treatment strategy for pediatric low-grade gliomas, playing a role in both early and late salvage treatments. Historically, for rapidly progressing or unresectable tumors, radiotherapy has been the primary treatment choice, with a 10-year progression-free survival (PFS) rate of 70% and overall survival (OS) rate of 80%. Radiotherapy is also used as adjuvant treatment for gliomas in special locations, such as the optic nerve pathway, hypothalamus, deep midline structures, and brainstem gliomas, where surgical options are limited to partial resection or biopsy. Current views suggest delaying the age at which radiotherapy is initiated to reduce the associated side effects, such as cognitive decline, endocrine dysfunction, secondary malignancies, cerebrovascular damage, and growth abnormalities, the severity of which highly depends on the tumor's location and the age at which treatment begins.

Chemotherapy regimens for newly diagnosed pLGG can achieve a PFS of 50% to 80% over three years. Currently, there is no definitive chemotherapy regimen for children with pLGG. In relevant single-center studies and randomized trials, the most common chemotherapy regimen is a combination of carboplatin and vincristine, while other randomized trial regimens have included combinations of thioguanine, procarbazine, lomustine, and vincristine, as well as combinations of carboplatin, vincristine, etoposide, or temozolomide. For children who show disease progression or symptoms after chemotherapy, reconsideration for surgical resection and age-stratified non-surgical treatments (chemotherapy + radiotherapy) can be made.

In the past five years, increasing clinical trials have shown that the use of molecular targeted drugs (such as BRAF inhibitors and MEK inhibitors) is effective in treating pLGG children who have failed first-line chemotherapy. However, the safety and optimal timing of molecular targeted therapies remain unknown and require further extensive clinical trials for validation.

4. What is a pediatric brainstem glioma?  

Brainstem gliomas exhibit significant heterogeneity in clinical characteristics, imaging features, anatomical locations, histological subtypes, and grading. Brainstem tumors account for 10-20% of all central nervous system tumors in children. Among brainstem gliomas, diffuse intrinsic pontine gliomas (DIPG) account for about 80%, with a very poor prognosis and a 2-year survival rate of approximately 10%. 10-15% of brainstem gliomas are low-grade gliomas with an indolent growth pattern. Currently, brainstem gliomas are primarily divided into five major categories: tectal glioma, DIPG, focal brainstem glioma, dorsal exophytic brainstem glioma, and cervicomedullary glioma.

Tectal gliomas account for about 5% of brainstem gliomas and are characterized as indolent, slowly growing tumors. Due to the tumor compressing the cerebral aqueduct, obstructive hydrocephalus often presents as the initial symptom, typically manifesting as headaches. However, because these tumors are classified as low-grade gliomas, they generally have a good prognosis, with a 10-year survival rate exceeding 90%. The imaging characteristics of tectal gliomas are very typical, and after imaging diagnosis, treatment usually focuses solely on addressing the hydrocephalus caused by the tumor. The first choice is endoscopic third ventriculostomy (ETV), followed by ventriculoperitoneal shunt; there is no need for routine tumor biopsy. If the tumor shows atypical imaging features or increases in size during follow-up after ETV, accompanied by relevant clinical symptoms, a biopsy may be warranted. If the tumor volume exceeds 3 cubic centimeters, shows enhancement or cystic changes, it may have a higher likelihood of progression, and more aggressive treatment options such as chemotherapy (for those under eight years old), radiotherapy (for those over eight), or surgical resection may be considered. Due to the tumor's location in the tectum, which contains multiple ascending and descending nerve fibers that manage eye movement, the probability of complete resection is low, and postoperative chemotherapy or radiotherapy may still be necessary.

5. What are the symptoms of brainstem gliomas?  

Common clinical manifestations of brainstem gliomas include cranial nerve dysfunction, long tract signs, and ataxia. Cranial nerve dysfunction results from damage to cranial nerve fibers or nuclei and can reflect the tumor's location and extent, providing diagnostic localization value. Long tract signs refer to clinical signs of involvement of long vertical fiber tracts within the brainstem, primarily including contralateral limb spastic paralysis, increased muscle tone, hyperreflexia, and positive pathological signs due to corticospinal tract injury; contralateral limb abnormalities in crude touch, pressure sensation, and pain temperature sensation due to spinothalamic tract injury; and contralateral limb abnormalities in conscious proprioception and fine touch due to medial lemniscus injury. Ataxia is mainly caused by damage to the cerebellar peduncles, while medial lemniscus injury can lead to sensory ataxia. If the tumor obstructs cerebrospinal fluid circulation pathways, it can result in supratentorial hydrocephalus, presenting with symptoms of increased intracranial pressure such as headaches, vomiting, optic disc edema, or optic nerve atrophy. Additionally, children with brainstem gliomas often exhibit atypical clinical symptoms that can appear months before the patient seeks medical attention, manifesting as irritability, aggressive behavior (primarily targeting parents), crying out or laughing in their sleep, excessive sweating, and difficulties with urination and defecation.