RU2236270C2 - Method for treating the cases of malignant cerebral tumors having multifocal growth pattern - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves applying photodynamic therapy and additionally irradiating remote cortical zones infiltrated with tumor using focused laser beam of 660 nm wavelength. Area of 1 cm² is exposed to radiation of power density of 0.53 W/ cm² and an area of 0. 5 cm² is exposed to radiation of power density of 2.4 W/ cm², respectively. Exposure time is equal to 295-450 s.

EFFECT: enhanced effectiveness of treatment.

Description

The invention relates to medicine, namely to neurosurgery, and can be used in the treatment of malignant brain tumors with a multifocal growth pattern with significant perivascular distribution and infiltration of the cerebral cortex at a distance from the location of the main node.

A known method of treating malignant brain tumors using remote radiation therapy (Zemskaya A.G., Leshchinsky B.I. Radiation treatment. In the book: Tumors of the brain of the astrocytic series. L .: Medicine, 1985, p.164-176) . The disadvantages of the method are: dependence on the radiosensitivity of the elements of the tumor, the correlation between its effectiveness and the volume of tumor removal, severe tolerance by a number of patients.

A known method of treating malignant brain tumors using photodynamic therapy (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 at the end of the operation with a scattered light beam, wavelength 400-800 nm, output radiation power 0.025-5.0 W, dose 1-300 J / cm ² . The disadvantages of the prototype are the locality of the impact, the ability to induce the death of tumor cells only in the resection zone to a depth of 3-12 mm, that is, the method is effective only when the tumor is located within one lobe and the majority of its volume is removed prior to its irradiation.

The invention is aimed at creating a method for the treatment of malignant brain tumors with a multifocal nature of growth, which allows to increase the efficiency of the method, while increasing the life expectancy of patients, to preserve its quality.

This is achieved by additional irradiation with a focused laser beam of areas of the cortex of small diameter affected by the tumor at a distance from the main node, including perivascular, which allows to achieve a greater degree of reduction of tumor cells, while avoiding additional surgical damage to the brain substance.

The introduction of a photosensitizer, its selective accumulation in tumor tissue and subsequent interaction with light in the presence of oxygen causes photochemically mediated cell destruction. The expected ratio of photosensitizer accumulation in the tumor tissue and brain substance is at least 4: 1, with a direct correlation between the level of its accumulation and the degree of tumor anaplasia. In addition, it is known that the level of penetration by light of biological tissue increases in proportion to an increase in the degree of cellularity of the latter. So in glioblastoma it is more than twice the level of penetration in normal tissue. Thus, photodynamic therapy contributes to additional reduction of tumor cells, while normal brain tissue remains intact.

The inventive method differs from the prototype in that it additionally irradiates areas of the cerebral cortex that are infiltrated by the tumor and are distant from the resection zone by a focused laser beam (exposure area of 1 cm or 0.5 cm) with a wavelength of 660 nm and a power density of 0.53 W / cm ² or 2.4 W / cm ^2, respectively, the irradiation time is 300-570 seconds and 75-145 seconds, respectively (dose 160-230 J / cm ² ).

The method is as follows. A second generation photosensitizer, photoditazine, is administered intravenously during intubation.

The dose of the drug is 5 mg per 1 kg of body weight. During the operation, the maximum possible removal of the tumor tissue is carried out depending on the location and nature of the tumor growth, after which the tumor bed is irradiated with a scattered laser beam. For this, a semiconductor laser with a radiation wavelength of 600-800 nm is used, the output radiation power at the end face of a six hundred micron quartz monofilament is 0.4 W, the power density is 0.13 mW / cm ² , the irradiation time is 1200-1800 seconds (dose 160-230 J / cm ² ). Irradiation of areas of the cerebral cortex infiltrated by the tumor tissue distant from the resection zone is carried out by focusing the laser beam of the fiber without the fiber touching the cortex. The power density is 0.53 W / cm ² or 2.4 W / cm ^2, respectively, the irradiation time is 300-570 seconds and 75-145 seconds, respectively (dose 160-230 J / cm ² ).

The inventive method is developed in RNHI them. prof. A.L. Polenov and Research Institute of Oncology. prof. N.N. Petrov and passed clinical trials in the treatment of a patient with a malignant brain tumor with a multifocal growth pattern.

Here is an extract from the medical history No. 2173-01: patient K., 35 years old, operation 10/06/2001, diagnosis: glioblastoma of the right frontal and temporal lobe, continued tumor growth. According to the claimed method, during intubation, a 2.5% solution of photoditazine in a dose of 4.8 ml was intravenously administered. During surgery, it was revealed that the tumor has a multifocal growth pattern: in addition to the main node, there are two foci of cortical infiltration at a distance. The main site was removed, the tumor bed was irradiated with a scattered laser beam with a wavelength of 660 nm, the power density was 0.13 W / cm ² , the irradiation time was 1200 seconds (dose 160 J / cm ² ), and then the focus of the light beam and phased irradiation of the changed areas crust, power density 0.53 W / cm ² , irradiation time 435 seconds (dose 230 J / cm ² ).

In the postoperative period, the patient had an increase in temperature to 38.6 on day 3-5. There were no other side effects. The wound healed by primary intention. Within 2 weeks after the operation, a complete regression of cerebral and partial regression of focal symptomatology was noted. Currently, the patient is alive, there are no signs of continued tumor growth. Observation continues. Using this method allowed:

- to avoid the development of additional neurological deficit in a patient with multifocal lesion of the cortex, including and functionally important areas;

- keep the patient well-being;

- to achieve an increase in the duration of the relapse-free period.

Claims (1)

A method for the treatment of malignant brain tumors with a multifocal growth pattern by photodynamic therapy, characterized in that they further irradiate areas of the cerebral cortex infiltrated by the tumor with a focused laser beam distant from the resection zone, the exposure area is 1 cm ² or 0.5 cm ² , wavelength 660 nm, power density 0.53 W / cm ² or 2.4 W / cm ² respectively, irradiation time 300-570 s or 75-145 s, respectively.