Multimodalty Treatment of Patients with Malignant Hemispheric Gliomas

V.E. Olyushin

Polenov Research Neurosurgical Institute, Saint Petersburg, Russia

 

Malignant gliomas account for 60% of all glial tumors. The last decades are characterized by improvement of the nearest results of their treatment. However, remote results and mean survival have undergone almost no changes. This index in patients with anaplastic astrocytomas and glioblastoma is 24 months and 12 months respectively.

Materials and Methods. We analyzed results of multimodality treatment of 231 cases with malignant hemispheric gliomas. Primary malignant tumors and tumors with prolonged growth were diagnosed in 119 and 94 patients respectively. A period of time between appearance of the first manifestations and hospitalization varied from 5 up to 8 months. On admission a subcompensated state was watched in a half of patients; every fifth case was in a severe state.

Multimodality therapy included surgical treatment, radiation therapy, chemotherapy, immunocorrection. Specific antineoplastic therapy and intraoperative photodynamic therapy (laser irradiation of a tumor bed with administration of a photosensitizer) were used in 23 and 13 cases respectively.

The surgery goal was maximum possible removal of a tumor, normalization of anatomic-physiologic functioning of the brain, exact histological diagnosis. Osteoplastic trephination was used in all patients. It was based on principles of reasonable radicalism and physiologic safety, which allowed to ensure a rather high life quality (the score of 70-80 according to Karnofsky's scale).

Chemotherapy with nitrosourea compounds was started in patients with malignant gliomas on the 4-10th day after operation and was repeated every subsequent 8 weeks. Radiation therapy with a total dose of 56-60 Gy was used in benign gliomas after compensation of a patient's state. Immunocorrection was carried out with application of various drugs (levamisolum, T-activin, timogen, timolin, neovir, glutoxim).

Postoperative specific antineoplastic therapy was used in 16 patients with a prolonged growth of glioblastomas and 7 cases with primary malignant gliomas, characterized by a different degree of anaplasia. It consisted in applying autologous dendrite cells with tumor antigens and activated lymphocytes of a patient.

Intraoperative irradiation of a tumor bed with a scattered laser beam was carried out in 13 cases (6 patients with primary gliomas and 7 patients with a relapse of malignant glioma). It was done against a background of administration of photoditazin (a home photosensitizer) 3-4 hours before operation. A prototype of a semiconductor laser (Atkus-2) with a wavelength of 660 nm was used. Irradiation duration and its dose were equal to 1200-1800 sec and 160-600 J/cm2 respectively.

Results. Postoperative mortality in patients with malignant gliomas was 2.7%. This index in reoperations for glioblastomas with a prolonged growth was 9.7%. Compensation of a state was watched in 97.3% of cases in the nearest postoperative period (1-5 days).

Chemotherapy did not result in marked complications. Moderate leucopenia and less frequent hyperchromic anemia developed after 4-5 courses of treatment and were corrected successfully by using appropriate therapeutic methods.

Radiation therapy, combined with chemotherapy, gave a reliable increase of a survival period in patients with malignant gliomas in comparison with the group without it. Immunocorrection had no effect on survival, but it allowed to improve a subjective state of patients, promoting quicker restoration of blood indices.

According to our data, specific antineoplastic therapy increased a mean period of survival in patients with a prolonged growth of glioblastomas after reoperation. It was 2 timed higher than in the control group (8.6 months and 4.5 months respectively). Besides, this therapy led to improvement of a functional status in 68% of patients.

The follow-up during 23 months revealed no prolonged growth in 3 patients with primary anaplastic astrocytomas, subject to photodynamic therapy. As for patients with primary glioblastomas, we watched no signs of a prolonged growth in 3 of them (a follow-up period of 4-5 months); a prolonged growth was diagnosed in 1 case a month after operation. Use of photodynamic therapy allowed to increase a relapse-free period in a half of cases with a prolonged growth of tumor after reoperation.

Conclusions. Use of new methods in multimodality therapy of hemispheric malignant gliomas (specific immunotherapy, photodynamic therapy), as well as creation of more active chemotherapeutic drugs allow to achieve improvement of remote results in a considerable number of patients.