Consensus on the treatment of low-grade glioma in children

Consensus on the treatment of low-grade glioma in children.  How to treat low-grade glioma in children?

Brain tumors are the most common solid tumors in children and the main cause of childhood cancer-related mortality.

There are important differences in the distribution, pathology, molecular characteristics and treatment strategies of brain tumors in children compared with adults. Similar to adults, gliomas constitute most children with supratentorial parenchymal tumors. However, most adult intraparenchymal lesions are malignant gliomas, while children are mainly low-grade gliomas.

Adult low-grade gliomas usually develop into high-grade lesions, while childhood gliomas have fewer malignant transformations. This is the result of basic molecular and genetic differences between these tumor groups. For example, adult low-grade astrocytomas and high-grade gliomas caused by malignant progression often have IDH1 or IDH2 gene mutations.

ATRX and 1p19q are both deleted, and IDH mutations are rare in children with low-grade gliomas outside of adolescence. Similarly, adult malignant gliomas often exhibit TP53 mutations, while this is much rarer in children with low-grade gliomas.

As the understanding of the molecular and genetic characteristics of childhood brain tumors becomes more and more detailed, treatment is guided by tumor classification based on comprehensive phenotypic and genotype parameters, and more and more molecular-oriented therapies are available. The World Health Organization (WHO) now recognizes that many tumor subgroups respond to different treatments.

For example, when it is determined that pilocytic astrocytoma is mostly caused by genetic changes in the mitogen-activated protein kinase (MAPK) signaling pathway, the treatment has changed dramatically. The most common is the BRAF gene as a therapeutic target. The further understanding of many other tumor molecular and gene maps has opened up many open ways for the research of targeted therapy.

Consensus on the treatment of low-grade glioma

Surgical resection is still the main method for the treatment of low-grade gliomas. Since 1970, the 5-year relative survival rate for pediatric central nervous system tumors has improved, from 57% to 74%.

As the survival rate of children after removal of particularly high-risk tumors increases, clinical standard postoperative radiotherapy and conventional chemotherapy have been replaced by a more subtle method to reduce the incidence of adjuvant therapy.

A risk-adapted treatment plan is adopted for tumors with favorable prognosis, and molecular targeted therapy broadens the medical options for lower-risk and favorable lesions.

The main purpose of surgery is to obtain tissue to establish a histopathological diagnosis, and to remove the tumor as much as possible without introducing any new neurological dysfunction. Whenever possible, total resection should be our goal. Generally speaking, for low-grade gliomas, the 10-year progression-free survival (PFS) of total total resection exceeds 85%, and the 10-year progression-free survival (PFS) of subtotal resection is less than 50%.

Therefore, for pilocytic astrocytoma, even the subcortical area, superficial non-pizziocytic astrocytoma and benign neuroepithelial tumors, because gross or near total resection has the main prognostic advantage, special attention should be paid to as complete as possible Removal of the tumor. For low-grade gliomas that are ill-defined, non-hairy, infiltrate into the deep nucleus or other visible areas, or cross the midline, total resection cannot be performed.

In these cases, image-guided stereotactic biopsy or open decompression in the case of larger lesions with mass effects will be more appropriate.

Principles of adjuvant treatment of low-grade glioma

Children with low-grade gliomas have a good prognosis after preoperative total resection and are not suitable for early adjuvant treatment. The 5-year survival rate of children with incompletely resected low-grade gliomas exceeds 90%. The results for adults are significantly worse, and this difference may reflect the fundamental difference in disease biology between the two age groups. While adult low-grade gliomas tend to undergo malignant degeneration, and some children with sub-total resection of low-grade gliomas remain static for a long period of time.

Due to the low incidence of low-grade gliomas in children, the exact incidence of malignant transformation is difficult to characterize. A study identified 11 patients who were initially diagnosed with grade 1/2 glioma or grade 2 astrocytoma, who developed malignant transformation to glioblastoma or other high-grade gliomas at a median time of 5.1 years .

All the risk factors analyzed, including radiotherapy, were not related to malignant transformation. Although a small number of children with malignant transformation precludes an accurate estimation of the rate of malignant progression, the long-term risk of malignant transformation of WHO grade 2 invasive astrocytoma has been proven to be less than 10%. The incidence of older children seems to be higher than that of all patients, but in the case of a small sample size, no significant difference was found.

Sum up

In general, the development of surgery and imaging techniques, conformal radiation therapy, and conventional chemotherapy has promoted the treatment of low-grade gliomas and improved the prognosis. Surgery is still the first choice for the treatment of tumors in the brain and cerebellar hemispheres, and the long-term survival rate is high after total resection.

Unfortunately, for deep tumors, such as optic gliomas, it is usually impossible to perform complete surgical resection.

Historically, radiotherapy has been used as a salvage treatment for progressive deep tumors, but because tumors are usually midline, large, and occur in young children, they are associated with cognitive and endocrine diseases.

Recently, people’s interest has focused on the use of conventional chemotherapy to delay or avoid the neurotoxic effects of radiation. Technological advances in radiation oncology have also reduced the incidence of necessary radiotherapy.

In the past decade, the availability of a large number of drugs that inhibit the MAPK pathway has led to promising results in phase I and phase II trials, and laid the foundation for the recent development of phase III studies in the childhood oncology group to compare molecular targeting Treatment and the best conventional chemotherapy regimen.

Other molecular targeted therapies are currently being studied, which provides hope for the future to see a large number of new therapies to further improve the treatment of low-grade gliomas in children.

(source:internet, reference only)

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