RU2318480C1 - Method for increasing photodynamic choroidea melanoma therapy effectiveness - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves intravenously introducing chlorine row photosensitizer at a dose of 0.8-1.0 mg/kg during 10 min after having exposed the tumor. Fluorescent diagnostic study of photosensitizer accumulation in tumor and in surrounding air is carried out after 15-20 min long exposure away from light. Electrodes are intravitreally introduced into the tumor and electrochemical lysis is carried out with 12-18 Q charge. The electrodes are withdrawn and intravitreal tumor laser-mediated irradiation is applied at wavelength corresponding to photosensitizer light absorption maximum field-by-field with neighboring fields overlap as follows. Tumor periphery is irradiated with intact tissue being caught not less than 1 mm far from ophthalmoscopically visible tumor boundary at power density of 40-60 J/cm² per 1 field. Then, one or several fields are irradiated by applying power density of 110-150 J/cm² to tumor top. Irradiation being over, tumor destruction products are removed.

EFFECT: complete tumor destruction; prevented tumor dissemination.

Description

The invention relates to medicine and can be used in ophthalmology to increase the efficiency of photodynamic therapy of melanomas of large choroid of size with a prominence of more than 8 mm

Choroid melanoma (MX) is one of the most common intraocular neoplasms, accounting for almost 80% of the total. MX is characterized by an extremely unfavorable prognosis both in relation to visual functions and the patient's life. The mortality rate for large melanomas is 53%.

One of the promising treatments for MX is photodynamic therapy (PDT). The PDT method is based on the selective accumulation of the introduced systemic photosensitizer (PS) in the vessels and stroma of the tumor, which upon subsequent laser irradiation with a wavelength corresponding to the absorption peak of this PS leads to phototoxic damage to the vascular system of the neoplasm and the death of tumor cells that accumulate PS.

It has been shown that the traditional photodynamic therapy of choroid melanoma, including intravenous administration of a photosensitizer and laser irradiation of the neoplasm (Barbazetto IA, Lee TC, Rollins IS, Chang S, Abramson DH. Treatment of choroidal melanoma using photodynamic therapy. Am J Ophthalmol. - 2003. - Vol.135. - No.6. - P.898-899) gives certain positive results, but in half the cases it is not possible to stop the growth of the intraocular neoplasm.

The effectiveness of PDT is limited by the height of the choroid melanoma, which is subject to experimental studies. Thirty-two New Zealand rabbits with pigmented choroid melanomas performed PDT (Kim RY; Hu LK; Foster BS; Gragoudas ES; Young LH. Photodynamic therapy of pigmented choroidal melanomas of greater than 3 mm thickness // Ophthalmology. 1996 Dec; 103 (12) : 2029-36): a chlorine-type PS was administered intravenously at a dose of 1 mg / kg, after which an intraocular neoplasm was irradiated transpillary. The dose of laser radiation ranged from 60 to 120 J / cm ² . The results of histomorphological studies confirmed the ability of PDT to destroy choroid melanomas with a thickness of not more than 4.6 mm. An earlier similar study (Gonzales VH, Hu LK, Theodossiadis PG, et al. Photodynamic therapy of pigmented choroidal melanoma // Ophthalmol Vis Sci. 1995; 36: 871-878) showed the effectiveness of PDT against pigmented choroid melanomas no more than 4.8 mm.

It is known that a photosensitizer accumulates in tumor cells with a fast cell cycle (fast metabolic processes). If there are cells in the tumor tissue that, at the time of treatment, the drug had not captured or accumulated in small quantities, the chances of their effective destruction are significantly reduced.

Thus, it is necessary to look for ways to increase the effectiveness of photodynamic therapy of choroid melanomas, especially large ones.

Electrochemical lysis does not have PDT-like efficacy limitations on tumor height. In addition, it was found that during the electrochemical lysis of neoplasms, the microvascular bed is blocked, and in the cathode field the capillaries are blocked as a result of electroosmotic fluid transfer, and in the anode field due to microthromboses (Matveev N.L., Kaplan M.A., Borsukov A.V. Technique and technique for the use of electrochemical lysis in the treatment of neoplasm: Recommendations for interventional radiologists, hepatobiliary surgeons, oncologists. - 2005. - P.14.). Therefore, electrochemical lysis can help block the photosensitizer circulating in the vascular bed, inside the tumor.

The authors do not know how to increase the effectiveness of photodynamic therapy of choroid melanoma.

The objective of the invention is to provide a method for increasing the effectiveness of photodynamic therapy of choroid melanoma.

The technical result is the complete destruction of the tumor, the prevention of metastasis.

The technical result is achieved by the fact that in a method for increasing the photodynamic therapy of choroid melanoma according to the invention, after a vitrectomy with maximum removal of the vitreous body and exposure of the tumor, a chlorine-type photosensitizer (PS) at a dose of 0.8-1.0 mg / kg is administered for 10 minutes, after exposure for 15-20 minutes without access to light, a fluorescence diagnosis of PS accumulation in the tumor is carried out and electrodes are intravitreal introduced into it in the air: anode and cathode and electrochemical lysis with a charge of 12-18 C (the charge passed through the conductor during the lysis) for 10 minutes, the electrodes are removed, then intravitreal laser irradiation of the tumor is carried out with a wavelength corresponding to the maximum absorption of PS light radiation, fields (3 mm in diameter), overlapping adjacent fields at 30% of area, as follows: the periphery of the tumor is irradiated with the capture of healthy tissue is not less than 1 mm from ophthalmoscopically visible tumor borders with an energy density per field 40-60 J / cm ^2, then one or more floor E (depending on the area of the vertex of the tumor) with an energy density of 110-150 J / ^cm2 was irradiated vertex tumor after irradiation degradation products removed tumor.

The technical result is achieved due to the fact that:

1) the chlorine-type PSs used are characterized by a high degree of purity, low toxicity, and the ability, even in small doses, to exhibit high photochemical activity under laser irradiation;

2) the time interval of 15-20 minutes between the introduction of PS and electrochemical lysis allows PS to accumulate in the tumor;

3) electrochemical lysis causes the destruction of the tumor in the volume of tissue around and between the electrodes, and also contributes to the blocking of the previously introduced and received FS in the tumor;

4) intravitreal laser irradiation of the neoplasm with a wavelength corresponding to the maximum absorption of light by the photosensitizer (intravitreal PDT), leads to the death of the remaining viable tumor cells outside the lysis zone, prevents the dissemination of tumor cells and metastasis;

5) removal of tumor destruction products allows to achieve anatomical correspondence of intraocular structures.

The claimed technical result can be obtained only by using the totality of the techniques proposed by us method.

The method is as follows.

A vitrectomy is performed with maximum removal of the vitreous body, the posterior hyaloid membrane is removed, the tumor is exposed and the tumor is exposed, the fluid-air is replaced, then a chlorine-type photosensitizer (PS), for example, photolon, photoditazine, radachlorin, is administered at a dose of 0.8-1, 0 mg / kg for 10 minutes, after exposure for 15-20 minutes without access to light, a fluorescence diagnosis of PS accumulation in the tumor is carried out and electrodes are introduced intravitreal into it: anode and cathode - and electrochemical lysis is performed with a charge of 12-18 C (charge that passed through the conductor during the lysis) for 10 minutes, the electrodes are removed, then intravitreal laser irradiation of the tumor is carried out with a wavelength corresponding to the maximum absorption of PS of light radiation, for example, with a wavelength of 662 nm for PS of the chlorine series, fields (diameter 3 mm), with overlapping adjacent fields by 30% of the area, as follows: irradiate the periphery of the tumor with the capture of healthy tissue at least 1 mm from the ophthalmoscopically visible border of the tumor with an energy density of 40-60 J / cm ² per field, then one or more fields (depending on the area of the top of the tumor) with an energy density of 110-150 J / cm ² irradiate the top of the tumor. At the end of the irradiation, the products of tumor destruction by the vitreotome are removed, the retina is straightened with a perfluororganic compound (PFOS), restrictive endolasercoagulation of the retinotomy site is performed, and PFOS is replaced with silicone oil.

The invention is illustrated by the following data.

Clinical example. Patient Z., 62 years old. He entered the Kaluga branch of Eye Microsurgery with suspicion of neoplasm of the choroid of the right eye. According to the results of a comprehensive examination, the diagnosis was made: Melanoma choroid OD. Tumor localization - in the posterior pole of the eye. The size of the tumor according to ultrasound B-scan: base - 11 × 13 mm, the size of the prominence - 9 mm. During phage, a characteristic “spotted” fluorescence was detected.

Informed patient consent was obtained for PDT of choroid melanoma with an increase in its effectiveness according to the proposed method.

After exposure of the tumor, photolon was administered intravenously at a dose of 1.0 mg / kg for 10 minutes, after exposure for 15 minutes, fluorescence diagnostics of PS accumulation in the tumor was performed and electrodes were introduced intravitreal into it. Electrochemical lysis was performed with a charge of 18 C for 10 minutes, the electrodes were removed and the tumor was intravitreally irradiated with laser radiation with a wavelength of 662 nm, fields (3 mm in diameter), with overlapping neighboring fields over 30% of the area. The energy density per field during irradiation of the periphery of the tumor with the capture of healthy tissues not less than 1 mm from the ophthalmoscopically visible border of the tumor with an energy density of 40 J / cm ² when irradiating the top of the tumor - 110 J / cm ² . At the end of the irradiation, the products of tumor destruction by the vitreotome were removed, the retina of PFOS was straightened, the endolaser coagulation of the retinotomy site was performed, PFOS was replaced with silicone oil.

During the control ultrasound examination after 6 months, a dense scar up to 1 mm thick was determined at the site of the neoplasm. The observation period of 2 years - without relapse and metastases.

The proposed method was applied in 7 patients with MX with a glimpse of more than 8 mm. Photolon or radachlorin or photoditazine in doses of 0.8 to 1.0 mg / kg were used as PS. Exposure without access to light - from 15 to 20 minutes. Electrochemical lysis was performed with a charge of 12 to 18 C for 10 minutes. When conducting intravitreal laser irradiation of the tumor, the energy density during irradiation of the periphery with the capture of healthy tissue by at least 1 mm was from 40 to 60 J / cm ² , when irradiating the top of the tumor from 110 to 150 J / cm ² . Overlap of the laser radiation fields occurred on 30% of the area to ensure uniform exposure. The observation period is from 10 to 24 months. In all cases, the achievement of the claimed technical result was noted.

Thus, the claimed method allows to achieve complete destruction of the tumor, to prevent metastasis.

Claims (1)

A way to increase the effectiveness of photodynamic therapy of choroid melanoma, which consists in the fact that after exposure of the tumor, a chlorine-type photosensitizer (PS) is administered intravenously at a dose of 0.8-1.0 mg / kg for 10 minutes, after exposure for 15-20 minutes without access to light they conduct fluorescence diagnostics of PS accumulation in a tumor and electrodes are intravitreal introduced into it in air and electrochemical lysis is performed with a charge of 12-18 C, the electrodes are removed, then the tumor is intravitreal irradiated with a wavelength corresponding to maximizing the absorption of PS of light radiation, with fields overlapping adjacent fields as follows: irradiate the periphery of the tumor with the capture of healthy tissue at least 1 mm from the ophthalmoscopically visible border of the tumor, with an energy density of 40-60 J / cm ² per field, then one or several fields with an energy density of 110-150 J / cm ² irradiate the top of the tumor, at the end of the irradiation, the products of tumor destruction are removed.