RU2318542C1 - Photodynamic therapy method for treating glial tumors in large cerebral hemispheres - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves intravenously introducing photosensitizer before surgical intervention and irradiating removed tumor bed with laser. Controllable hyperoxia state is created during exposure by increasing partial pressure of oxygen in air-and-oxygen mixture to 60%. Blood acid-base balance values central hemodynamic parameters are controlled.

EFFECT: enhanced effectiveness of treatment.

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Description

The invention relates to medicine, namely to neurosurgery, and can be used in the complex treatment of patients with glial tumors of the cerebral hemispheres of various degrees of malignancy, including those with a multifocal growth pattern and significant perivascular distribution, as well as cerebral cortex infiltration far from the primary node.

Glial brain tumors make up 50-60% of all tumors of the central nervous system. Currently, the universally recognized standard in the treatment of patients with supratentorial localization glial tumors is an integrated approach, the basis of which is surgical treatment. As adjuvant therapy, radiation therapy, chemotherapy, immunotherapy, and photodynamic therapy are used.

The main efforts to create new and improve existing methods of antitumor therapy are aimed at achieving the maximum possible targeted therapeutic effect. One such method is photodynamic therapy.

Closest to the claimed method is a method of photodynamic therapy for the treatment of glial brain tumors (Popovic E.A., Kaue A.N., Hill JS: Photodinamic therapy of brain tumors. Semin. Surg. Oncol. 11: 335-345, 1995 ) adopted by us for the prototype. The method involves the intravenous administration of a photosensitizer before surgery, the maximum possible removal of tumor tissue and subsequent irradiation of the bed of the removed tumor with a laser, wavelength 400-800 nm, output radiation power of 0.025-5.0 W, light dose of 1-300 J / cm ² .

A significant disadvantage of the prototype, reducing its effectiveness, is the following circumstance. The main part of the cells of the perifocal region of glial tumors, which is a direct object of photodynamic therapy, due to the characteristics of metabolism, is in conditions of hypoxia. At the same time, the intensity of the photodynamic interaction is directly dependent on the concentration of oxygen in the biological medium.

The invention is aimed at creating a method of photodynamic therapy for the treatment of glial tumors of the cerebral hemispheres, which allows to increase the effectiveness of photodynamic therapy by increasing oxygenation in the perifocal zone of the tumor.

The specified technical result in the implementation of the invention is achieved by the fact that in the known method of photodynamic therapy for the treatment of glial tumors of the cerebral hemispheres, including the intravenous administration of a photosensitizer before surgery and irradiation of the bed of the removed tumor with a laser, the peculiarity is that during irradiation they create controlled hyperoxia by increasing the partial pressure of oxygen in the oxygen-air mixture to 60% during total intravenous th anesthesia under the control of indicators of the acid-base state of the blood and parameters of central hemodynamics.

Photodynamic therapy is carried out in oxygenated tumor tissue. This is achieved by increasing the oxygen tension in the patient’s blood by increasing the partial pressure of oxygen in the oxygen-air mixture during total intravenous anesthesia.

The method is as follows. A photosensitizer of a group of chlorins e of the II generation, in particular Photoditazine, is administered to the patient in the preoperative period 1 hour before irradiation of the tumor bed intravenously in a dose of 0.5 mg / kg of the patient’s body weight. Anesthetic management of surgical intervention is carried out by conducting total intravenous anesthesia with controlled breathing. Surgically produce the maximum possible removal of the tumor, carry out the final hemostasis. Then, a neurosonographic study is performed, during which the size and shape of the bed of the removed tumor is specified, in accordance with which the parameters of laser radiation are determined from the calculation of 150 J / cm ² . By the time radiation begins, the oxygen content in the inhalation mixture is increased to 60%. Then, in accordance with the calculated dose, the bed of the removed tumor is irradiated with a laser. The source of laser radiation is a semiconductor laser with a wavelength of 661 nm. At the end of the irradiation, the composition of the oxygen-air mixture is restored to its original values. Before, during and after hyperoxia, blood gas composition and central hemodynamic parameters are monitored to monitor tissue perfusion and to eliminate the toxic effects of oxygen.

The inventive method is developed in the Federal State Institution Russian National Scientific Research Institute named after prof. A.L. Polenova and passed clinical trials in the treatment of 15 patients with glial tumors of the cerebral hemispheres. An analysis of the immediate results of treatment indicates an increase in the time of a relapse-free period and the life expectancy of this category of patients.

We give an example - an extract from the medical history No. 1741/04.

Patient I., born in 1944, was admitted to the clinic of the institute on July 28, 2004 with a suspected tumor of the right temporal lobe in a compensated state (80 points on the Karnofsky scale). The clinical picture is represented by epileptic syndrome with frequent seizures of two types: 1) simple partial sensory olfactory; 2) simple partial seizures with a violation of mental functions of the type deja etendu. Focal symptoms are represented by insufficiency of the left VII, XII cranial nerves, left-sided pyramidal insufficiency.

When examined by a neurophthalmologist, visual acuity is: VISOD = 0.3 s + 1.0 = 0.4; VISOS = 0.9-1.0. There is no stagnation in the fundus. The field of view is not changed.

On MRI of the brain dated July 10, 2004, in the mediobasal parts of the right temporal lobe, a volumetric formation is determined without clear contours of 46 × 35 × 39 mm. The zone of perifocal changes is moderate. The displacement of the middle structures from right to left by 25 mm. The subarachnoid convexital space of the right hemisphere is compressed, the left - expanded.

08/02/2004 the operation was performed: osteoplastic trepanation of the skull in the right frontotemporal-parietal region, subtotal removal of the tumor from the projection transcortical access. According to the claimed method, 1 hour before irradiation of the tumor bed, Photoditazine was administered intravenously in a dose of 32 mg. Total intravenous anesthesia with artificial ventilation of the lungs using the KION apparatus along a semi-open circuit was used. During the operation, osteoplastic trepanation of the skull was performed in the right frontotemporal-parietal region with additional resection of the temporal bone scales. Out-of-projection access to the tumor was made through the posterior sections of the middle temporal gyrus. The tumor is subtotally removed. The surface area of the bed of the removed tumor was 16 cm ² . In accordance with the protocol, photodynamic therapy was carried out (light dose of 150 J / cm ² ). By the beginning of the irradiation, the oxygen content in the inhalation mixture was increased to 60%. Then, in accordance with the calculated dose, the bed of the removed tumor was irradiated with a laser: wavelength 661 nm, laser radiation power 2 W, duration 20 minutes. At the end of the irradiation, the composition of the oxygen-air mixture was restored to its original values. The results of the study of the acid-base state of capillary blood and the parameters of central hemodynamics are as follows:

Indicators Source During hyperoxia After hyperoxia pH 7,368 7,356 7,349 pCO ₂ , mmHg 42.5 43.6 44.9 BE, mmol / l -1.4 -1.7 -1.6 BE ecf, mmol / L -1.3 -1.6 -1.3 BB, mmol / l 46.6 46.2 46,4 HCO ₃ , mmol / l 23.9 23.8 24.2 pO ₂ , mmHg 77.3 186.6 65.9 O ₂ , sat% 94.7 99.5 91.4 Heart index 3.2 2.9 3.0

Thus, during controlled hyperoxia during photodynamic therapy, indicators of homeostasis and central hemodynamics do not go beyond physiological parameters.

The early postoperative period in the patient proceeded safely: there were no clinical manifestations of the epileptic syndrome, there was no increase in focal symptoms. The postoperative wound healed by first intention, the sutures were removed on the tenth day. Local and systemic phototoxic effects were also not observed. The result of the histological conclusion: fibrillar-protoplasmic astrocytoma. The patient was discharged in a compensated state (80 points on the Karnofsky scale).

Follow-up information about the patient for the period January 2006 is as follows. No complaints of headache. Single rare (1 time in 2-3 months) simple partial seizures with a violation of mental functions of the deja etendu type are noted. In a clinical study, there is no evidence for continued tumor growth. MRI of signs of continued tumor growth was also not detected. The patient works in the same place. There are no violations of domestic and social adaptation.

Using the proposed method allows to increase the effectiveness of photodynamic therapy by creating the most optimal biological conditions for the implementation of photodynamic action, to increase the life expectancy of patients and improve its quality.

Claims (1)

A method of photodynamic therapy for the treatment of glial tumors of the cerebral hemispheres, including the intravenous administration of a photosensitizer before surgery and laser irradiation of the bed of the removed tumor, characterized in that during irradiation they create controlled hyperoxia by increasing the partial pressure of oxygen in the oxygen-air mixture to 60% under monitoring indicators of the acid-base state of the blood and the parameters of central hemodynamics.