Treatment of brain tumors in children

Surgical treatment of brain tumors in children

The standard and key method of treating CNS tumors is surgical removal. Over the past three decades, the survival rate of patients with CNS tumors has improved significantly due to the advent of modern diagnostic methods (widespread use of magnetic resonance therapy with contrast enhancement), improvement of neurosurgical techniques, neuroanesthesiology and resuscitation, and improvement of accompanying therapy.

Neurosurgery plays a leading role in the treatment of patients with brain tumors. The operation allows for the maximum removal of the tumor and resolution of problems associated with the mass effect (symptoms of intracranial hypertension and neurological deficit), i.e., elimination of the immediate threat to the patient's life, as well as obtaining material to determine the histological type of the tumor. Macroscopically complete removal of the tumor is of particular importance, since the results of treating patients with a totally removed neoplasm are better than the results of treating patients with a large residual tumor. The completeness of tumor removal is determined based on the operation protocol and comparison of CT and MRI data before surgery and 24-72 hours after its completion.

Stereotactic biopsy is indicated for inoperable tumors in order to establish the histological type of the neoplasm.

Radiation therapy for brain tumors in children

Radiation therapy is another important component of treatment for children with brain tumors. Determining the optimal dose and radiation fields depends on the size and location of the tumor, as well as its expected spread. Total CNS irradiation is used when there is a high probability of tumor spread via the cerebrospinal fluid flow.

For most tumors, the radiation dose is determined by the need to control the tumor and the tolerance of normal brain tissue. Tolerance depends on a number of factors, including the anatomical location (the brainstem and thalamus are most sensitive to radiation), the radiation dose, and the child's age. Doses of 54 Gy, 45 Gy, and 35 Gy, administered 5 days a week daily in fractional doses (1.6 to 1.8 Gy for local fields of the brain and spinal cord, respectively), are used in children over 3 years of age, that is, when brain development is almost complete. In younger children, such doses can cause damage to nerve cells and delay mental and physical development. This is why radiation therapy is not performed on children under 3 years of age.

Polychemotherapy of brain tumors in children

Polychemotherapy plays an important role in the complex treatment of brain tumors in children. Thanks to its use over the past 20 years, treatment results have improved significantly. It is especially relevant for certain histological types of tumors in young children, for whom it is desirable to postpone or exclude radiation therapy completely, as well as for inoperable neoplasms and metastasis.

For a long time, the use of systemic chemotherapy for brain tumors was considered inappropriate and ineffective. Among the justifications for this point of view, the presence of the blood-brain barrier was in the first place. The blood-brain barrier slows down the penetration of high-molecular water-soluble drugs from the blood into brain tissue, while low-molecular fat-soluble substances easily overcome it. In fact, the blood-brain barrier is not a serious obstacle to conventional chemotherapeutic drugs, since its function is impaired in many brain tumors. Tumor heterogeneity, cellular kinetics, methods of administration and routes of drug elimination play a more significant role than the blood-brain barrier in determining the sensitivity of a particular tumor to chemotherapy. Tumors with a low mitotic index and slow growth are less sensitive to chemotherapy, while fast-growing tumors with a high mitotic index are more sensitive.

Since 1979, SIOP has been conducting experimental and clinical developments of methods for the complex treatment of brain tumors in children using chemotherapy. It has been shown that more than 20 modern cytostatics are effective in this situation, including nitrosourea derivatives (CCNU, BCNU, ACNU), methotrexate, cyclophosphamide, ifosfamide, etoposide, teniposide, thiotepa, temozolomide, as well as alkaloids of the pink periwinkle plant (vincristine, vinblastine) and platinum preparations. The introduction of chemotherapy drugs directly into the cerebrospinal fluid allows for a significantly higher concentration of drugs both in the cerebrospinal fluid and in the surrounding brain tissue. This method of administration is most applicable to young children with a high risk of metastasis along the cerebrospinal fluid pathways and the impossibility of radiation therapy.

Traditionally, chemotherapy is used as an adjuvant after surgery and radiation therapy.

Until recently, the use of chemotherapy in relapses was limited (only a few drugs were used). Currently, almost all authors point to the high immediate effectiveness of a combination of chemotherapy drugs in relapsed medulloblastoma (treatment effectiveness in the first 3 months is 80%).