RU2514107C1 - Method for photodynamic therapy of patients with metastatic tumoural pleuritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: photosensitiser Photosense is administered. The patient is irradiated with using an optical fibre with a lens on a distal end in contact with a chest wall along intercostal spaces in 8-10 random positions for 1 therapeutic session. A light dose of one position of the laser radiation is 100 J, and an output power is 200-250 mWt,.

EFFECT: method provides regression of the tumoural process, obliteration of the pleural cavity without the aggressive intrapleural intervention, and eliminates potential infections.

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Description

The present invention relates to medicine, namely to oncology, and can be used as a method of treating patients with metastatic tumor pleurisy.

Pleurisy - accumulation of exudate in the pleural cavity, as a complication of a number of diseases. The cause of pleurisy in cancer patients is a tumor lesion of the pleura, lungs. It can be both primary malignant tumors of the pleura - mesothelioma, and metastatic tumors.

Tumor lesion of the pleura causes local inflammatory processes, an increase in capillary permeability, a violation of the integrity of the lymphatic vessels. Cancer cells cause angiogenesis, ensuring the growth of new capillaries and neovascularization of the pleura, which increases the permeability of tissues and the expressed formation of exudate (Selchuk V.Yu. et al. “Tumor serosites.” Practical medicine. Moscow. 2011, pp. 27-28).

Tumor metastatic pleurisy is one of the most common complications of malignant neoplasms. In about half of patients with advanced forms of cancer, the course of the disease is complicated by the development of tumor pleurisy. In particular, the incidence of tumor pleurisy in lung cancer is 20–25%, in breast cancer - up to 48%, in lymphomas and leukemia - up to 26%, and in ovarian cancer - up to 10%. Exudate in the pleural cavity leads to compression of the lung, displacement of the mediastinum and, as a result, the presence of severe shortness of breath, impaired respiratory and cardiac activity. Often pleurisy is the only manifestation of the tumor process and can cause the death of the patient. Without treatment, the median life expectancy of a patient with tumor pleurisy is 4 months (Selchuk V.Yu. et al. “Tumor serositis.” Practical medicine. Moscow. 2011, p. 55). Treatment of this category of patients, aimed at stopping pleurisy, significantly increases the life expectancy of patients.

Maintaining a good quality of life for cancer patients is the main goal of therapy for advanced cancer of any location and can be achieved by reducing the symptoms of the disease (ESMO-2010).

The treatment of patients with metastatic tumor pleurisy presents certain difficulties and requires a strict individual approach. There is no single algorithm for treating patients with this pathology. In the treatment of patients with tumor pleurisy, therapeutic thoracocentesis, systemic drug therapy, intrapleural therapy, and long-term drainage of the pleural cavity are used.

Thoracocentesis - a puncture of the pleural cavity with the evacuation of exudate - is exclusively symptomatic therapy and in 98-100% of patients after 1 month there is a repeated accumulation of exudate. Systemic polychemotherapy is not effective enough. In particular, with breast cancer, ovary, small cell lung cancer, lymphomas can lead to the elimination of pleural effusion in 30-60% of patients. Intrapleural chemotherapy with the use of cytostatics is possible, as well as the use of sclerosing agents, which leads to obliteration of the pleural cavity (pleurodesis) and is a symptomatic treatment. However, such an aggressive intrapleural effect has a number of complications, and more than 30% of patients potentially considered candidates for pleurocentesis have contraindications for its implementation. Complications are manifested in the form of general intoxication and, as a consequence, renal, hepatic, cardiac and pulmonary insufficiency (Selchuk V.Yu. et al. “Tumor serositis. Practical medicine. Moscow. 2011, pp. 65-78).

Invasive intrapleural therapy has a number of significant disadvantages:

- intrapleural therapy is an aggressive intervention with the introduction of toxic agents into the pleural cavity in order to obliterate the cavity,

- the introduction of drugs for obliteration of the pleural cavity leads to general intoxication and a significant deterioration in the condition of patients,

- intrapleural exposure is accompanied by severe inflammatory processes in the pleural cavity,

- pleurodesis with the introduction of drugs into the pleural cavity for its obliteration is a purely symptomatic treatment,

- there is a high risk of complications in the treatment of patients with severe concomitant pathology of the heart, lungs, liver, and kidneys.

There is a method of intrapleural photodynamic therapy with the Photosens drug in patients with primary and metastatic pleural damage complicated by malignant pleurisy (Vursol D.A., dissertation for the candidate of medical sciences, Moscow, 2009, prototype), which consists in the fact that after Intravenous administration of a photosensitizer Photosens into the pleural cavity by thoracentesis is administered from 2 to 5 diffusers, then intrapleural irradiation of the pleural cavity is carried out daily for 5-7 sec nsov. When conducting treatment according to the proposed method, according to the results of the study, pleural cavity obliteration - pleurodesis was achieved in 93% of cases.

During PDT, the effect of not only pleural cavity obliteration as a palliative treatment was achieved, but also of partial regression of pleural malignant tumors.

The disadvantages of invasive intrapleural photodynamic therapy:

- intrapleural therapy is an aggressive intervention involving the injection of 2-5 diffusers and drainage into the pleural cavity by thoracentesis for up to 6-8 days,

- intrapleural exposure with prolonged presence of percutaneous drainage and diffusers can lead to infection of the pleural cavity and purulent process,

- the introduction of optical fibers into the cavity of the diffuser during daily laser irradiation may be accompanied by perforation of the diffuser channel (mechanical or thermal), which can cause additional infection of the pleural cavity,

- the patient is in bed for 6-8 days in the presence of installed drains and diffusers,

- treatment of patients using this technique is carried out only in a hospital setting.

The objective of the present invention was to develop such a treatment method that would eliminate aggressive intrapleural intervention, be organ-preserving, ensure no complications, and also create the possibility of treating patients on an outpatient basis even if there is a pronounced concomitant pulmonary and cardiac pathology.

The problem is solved as follows: after intravenous administration of the photosensitizer Photosens, irradiation is carried out by means of a fiber with a lens on the distal end in contact with the chest wall along the intercostal space in 8-10 arbitrary positions on the entire chest wall in 1 session, while the light dose of one exposure position 100 J, power 200-250 mW at the output of the fiber.

The proposed method is as follows. At the first stage, before the PDT, the patient is given a pleural puncture with evacuation of exudate. X-ray examination is desirable to clarify the localization of the pathological process. If necessary, pleural puncture is repeated during the course of treatment in case of accumulation of exudate (usually 7-8 days after the start of PDT). 1-2 days after pleural puncture, the photosensitizer is introduced. The drug before administration is diluted with 0.9% sodium chloride in a ratio of 1: 4. The photosensing solution is administered once intravenously by means of a 30-minute infusion at a dose of 0.3-0.4 mg / kg. 24 hours after the administration of Photosens, a contact PDT session is performed (RF patent No. 2275945, A61N 5/067, 2004). The pleural cavity is irradiated with a fiber with a lens with a diameter of 1 cm at the distal end, in contact with the chest wall along the intercostal space, 8-10 arbitrary positions on the entire chest wall for 1 treatment session. The light dose of one position of laser irradiation is 100 J, the output power of the fiber is 200-250 mW. The number of sessions (treatment days) is 9-10.

The proposed method is illustrated by the following examples.

Example 1

Patient P. 76 years. Diagnosis: cancer of the right breast T2, N1, M0, complex treatment in 1997, pleural metastases, right-sided pleural effusion. Before PDT, 1000.0 ml of pleural exudate was evacuated. 2 days after pleural puncture, a Photosens sensitizer was administered at a dose of 0.4 mg / kg. 24 hours after the administration of Photosens, a session of contact PDT was performed. The pleural cavity was irradiated by means of a fiber with a lens with a diameter of 1 cm at the distal end, in contact with the chest wall along the intercostal space, 8-10 arbitrary positions on the entire chest wall for 1 treatment session. The light dose of one position of the laser irradiation is 100 J, the output power of the fiber is 200-250 mW. Conducted 9 treatment sessions. As a result, stabilization of the process is achieved. After 2 months, a control pleural puncture evacuated 500 ml of residual fluid. X-ray control during 1.5 years of observation revealed persistent stabilization of the process. There are no complications.

Example 2

Patient B. 71 years. Diagnosis: cancer of the left breast T2, N0, M0, complex treatment in 2000, metastases in the pleura, left-sided exudative pleurisy. Before PDT, 1,500.0 ml of pleural exudate was evacuated. A day after pleural puncture, a Photosens sensitizer was introduced at a dose of 0.3 mg / kg. 24 hours after the administration of Photosens, a session of contact PDT was performed. The pleural cavity was irradiated by means of a fiber with a lens with a diameter of 1 cm at the distal end, in contact with the chest wall along the intercostal space, 8-10 arbitrary positions on the entire chest wall for 1 treatment session. The light dose of one position of the laser irradiation is 100 J, the output power of the fiber is 200-250 mW. Conducted 9 treatment sessions. As a result, stabilization of the process is achieved. After 1 month, with control pleural puncture, 250 ml of residual fluid was evacuated. X-ray control after 1 year of observation revealed stabilization of the process, pleural cavity obliteration, fibrosis. There are no complications.

Using the drug Photosens and laser irradiation according to the proposed method, 14 patients with oncological pathology of the pleura and the presence of uncurable pleurisy were treated. As a result, in 9 (64%) cases, stabilization of the process was registered - partial regression of tumors and obliteration of the pleural cavity. There were no complications associated with PDT.

Thus, the proposed method of treatment eliminates aggressive intrapleural intervention, is organ-preserving, ensures no complications, makes it possible to treat patients on an outpatient basis even in the presence of pronounced concomitant pulmonary and cardiac pathology, improves the quality of life of patients.

Claims (1)

A method for the photodynamic therapy of patients with metastatic tumor pleurisy, including the intravenous administration of a photosensitizer Photosens followed by laser irradiation, characterized in that the irradiation is carried out by means of a light guide with a lens on the distal end in contact with the chest wall along the intercostal space at 8-10 positions along the entire chest wall in one session, while the light dose of one irradiation position is 100 J, the output power of the fiber is 200-250 mW.