Results on complex treatment of patients with glial tumors of brain with local chemotherapy

Aim. For the purpose of local chemotherapy in patients with malignant brain tumors after partial or total removal of tumors we used biodegradable film with methotrexate. The film, due to its properties, is firmly attached to the wound surface. With its composition of chemotherapeutic agents over specified time, the dosed film immediately affects diseased tissue, playing the role of a local chemotherapy depo. Methods. Results of treatment of 74 patients with low differentiated gliomas of the brain, which have undergone a comprehensive treatment that includes surgical removal of tumor and implantation of methotrexate depo in the wall of postoperative cerebral injury followed by radiotherapy in the pig on a bed of the tumor removed. Results. A retrospective analysis of the results of complex treatment of patients with glial brain tumors with local chemotherapy showed a significant increase in disease-free period in patients who have undergone, consistently, surgery, chemotherapy and adjuvant local radiation therapy. Conclusions. Our research has shown that the use of local chemotherapy greatly improves the results of treatment of patients not only for total removal of intracerebral tumors, but also for subtotal removal, as well as in patients with prolonged tumor growth, when there is no possibility of radiation treatment.

Introduction.Intracerebral or glial tumors account for 50 % of all tumors of the central nervous system.Despite diagnostics improvement, a mortality of patients with intracerebral tumors remains high, and results of treatment are unsatisfactory.A role of adjuvant chemotherapy up to date has not been fully clarified.
We attempted to solve the problem of developing the most optimal way to deliver chemotherapeutic agents to partially resected tumor, or to the areas of previously removed brain tumor.Our studies on experimental animals indicated the preferred activation mechanisms of apoptosis in the drugs implanted films with methotrexate, compared to the drugs with a depot effect of cisplatin.
Low grade glioma (LGG) is a group of malignant brain tumors of neuroectodermal origin.According to the WHO classification, they include: anaplastic glioma (anaplastic astrocytoma, oligodendrogliomas and oligoastrocytomas) and glioblastoma multiforme.
Treatment of patients with low grade gliomas remains today one of the most pressing problems of neurosurgery and oncology.Despite using practically entire arsenal of anticancer therapies and surgical techniques, the average life of patients with LGG usually does not exceed 12 months.
From biological viewpoint on tumoral growth, LGG represents the local process that affords a possibility of wide application of local methods of anticancer therapy at this disease.The local chemotherapy is the most perspective in this respect.
In both domestic and foreign literature there are numerous publications regarding clinical experience with solutions of various anticancer drugs for local chemotherapy, but the results were not very comforting.In recent years, some investigators attempted to use the brain-polymer formulations of cytotoxic drugs deposited in resorbable polymers for local chemotherapy of non-differentiated gliomas.
Materials and methods.For local chemotherapy of patients with glial brain tumors after partial or total removal of tumors we used self-resolving film with methotrexate.One option for the localization of anticancer drugs may be their deposition in the polymer matrix (biodegradable), and the tool itself realized in the form of a multilayer polymeric film, affixed to the affected area.
Successful application of a polymer adhesive selfresolving film of «diplen» in medical practice allowed us to use the latter as a basis for creating anticancer drug depot with the cytostatic methotrexate.
The films, due to their properties, are firmly attached to the wound surface.With the composition of chemotherapeutic agents over a specified time, the films being resolvable and dosed, directly affect the diseased tissue, playing the role of a depot chemotherapy.
74 patients with the brain LGG had undergone a comprehensive treatment that included surgical removal of the tumor within the intact brain tissue, or after subtotal removal, with implantation in the wall of the postoperative brain injury depot methotrexate followed by radiotherapy in the total focal dose in resected tumor bed of 60 Gy.80 patients in the control group had undergone a standard combination therapy consisting of similar surgery and radiation therapy on ODS in the removed tumor region (60 Gy).
For histological classification the tumors were assigned to the following groups: anaplastic astrocytoma -30; anaplastic oligoastrocytomas -14; anaplastic oligodendrogliomas -9; glioblastoma -21.The pa- The studied and control groups tients' age from 10 to 78 years.The median age was 50 years.There were 38 men, 36 women.In the group studied 48 patients received complex treatment: surgery with total or subtotal resection of tumor and implantation of the polymer film with methotrexate for the local chemotherapy and adjuvant radiation therapy.
The remaining 26 patients underwent only surgery with implantation of the polymer film with methotrexate, and postoperative radiation therapy was performed.Of the 74 patients studied, 23 with continuing growth of the previously removed malignant brain tumor were operated on.This group consisted mostly of the patients who did not receive postoperative radiation therapy, as they completed the full course of radiation treatment after the first operation.The remaining 3 patients, for various reasons, refused radiotherapy.
An assessment of the overall condition of the patients on admission was made on a scale of Karnoffskiy and ranged from 40 % to 80 %.
The operations were performed under general anesthesia.Of 74 patients in 61 the tumor was removed within a macroscopically visible healthy tissue, in 13subtotally.
Results and discussion.Our study showed that the patients with glial structures of the brain consist 50 % of the total number of neuro-oncology patients.The most aggressive in terms of recurrence of the tumor is anaplastic astrocytoma.
A comparative analysis of relapse-free period between the studied and control groups is presented in the Table .A retrospective analysis of the results of complex treatment of patients with glial brain tumors with local chemotherapy showed a significant increase in diseasefree period in the patients who have undergone, consistently, surgery, chemotherapy and adjuvant local radiation therapy.
Our research has shown that the use of local chemotherapy greatly improves the results of treatment of patients not only for total removal of intracerebral tumors, but also for subtotal removal, as well as in pati-ents with prolonged tumor growth, when there is no possibility of radiation treatment.
Thus, we examined the results of complex treatment of patients with glial brain tumors using the method of local chemotherapy.Given these results, we believe further research is very promising in this regard.