section Home
Production, Amateur
Radio amateur
Model aircraft, rocket-
Useful, entertaining 		Stealth master
Electronics
Physics
Technologies
invention 		space Mystery
Earth Mysteries
Secrets of the Ocean
Stealth
section Map
Start
Forum
Use of material is permitted for reference (for websites - hyperlinks)
INVENTION
Russian Federation Patent RU2286817

METHOD COMBINED treatment of locally advanced malignant tumors of the trachea and / or bronchitis

Name of the inventor: Mark L. Gelfond (RU); Andrey Ivanovich Arseniev (RU); Young Master Alex Stepanovich (RU); Alexander Shcherbakov (RU); Kanaev Sergey (RU); Shulepov Veniaminovich Alexander (RU)
The name of the patentee: VCO Oncology Institute. prof. NN Petrov, the Ministry of Health (RU)
(98) Address for correspondence: 197758, St. Petersburg, Sand Str. Leningradskaya, 68, VCO Oncology Institute. prof. NN Petrova Health Ministry
Address for correspondence: 197758, St. Petersburg, Sand Str. Leningradskaya, 68, VCO Oncology Institute. prof. NN Petrova Health Ministry
Starting date of the patent: 2004.07.06

The invention relates to medicine and can be used in the treatment of oncological diseases, namely, locally advanced tumors of the trachea and / or bronchi. Argon carried recanalization of the lumen of the trachea and / or bronchi at a power of 60-90 watts, followed by brachytherapy source when motion trajectory length of 5-20 cm, step 5 mm and a depth of 10 mm isodose reference to the source. Provide movement above and below the applicator tumors 1 to 3 cm and summing the dose 14 to 28 Gy in mode 1 time per week to 7 Gy. Carry out external beam therapy mode 5 times a week for up to 1-2 Gy SOD doses of 45-55 Gy. Additionally, prior to radiotherapy, photodynamic therapy is carried out with a preparation "photodithazine" 0.8-1.5 mg / kg, and the radiation of a semiconductor laser wavelength of 662 nm and a total energy dose of 400 J. The method allows to achieve reduction of tumor mass, to restore airway ways to reduce the toxicity and pain.

DESCRIPTION OF THE INVENTION

The invention relates to methods of treating cancers, namely malignant tumors of the trachea and the central bronchi.

Malignant tumors are the most acute medical and social problem. Cancer incidence has been steadily increasing. The Russian contingent of patients with malignant neoplasms of more than 2 million people, ie 1.5% of the population. WHO experts believe that the upward trend in cancer incidence around the world will be saved, and to 90% of patients some tumor localization processes are incurable. Of these, 70% of the needs of palliative care and, as a rule, does not get it (DV Kudryavtsev et al superfractionation non small cell lung cancer radiotherapy // Russian Journal of Oncology -.. 2003. - №2 -. S.10- 14; BK Poddubny, MI Davidov et al Bronchoscopy in the palliative treatment of patients with lung cancer // Herald RCRC - 2003. - №1 - S.33-36)....

Lung cancer is one of the first places among the morbidity malignant neoplasms. In Russia, it is in second place in the overall structure of the cancer and on the ground (31%) among malignant tumors in men. Every year registered more than 63,000 cases of lung cancer and die from it 60,000 people in Russia. In St. Petersburg, and it maintains one of the highest rates of cancer incidence. Thus, the statistics show that lung cancer is one of the most common and is usually characterized by a poor prognosis malignant disease (McDuffie HH, Klaassen DJ, Dosman JA Female-Male differences in patients with primary lung cancer // Cancer 1987; 59 ...:. 1825-1830; Martini N., Bains M., Burt M. et al Incidence of local recurrence and second primary tumours in resected stage I lung cancer // J. Thorac Cardiovasc Surg - 1995. - Vol.109 . - P.120-129; Landis SH, Murray T, Bolden S., Wingo PA Cancer Statistics, 1999 // CA Cancer J Clin 1999; 49: 8-31).

In recent years, medicine was recognition of the fact that the functional parameters (in the broad sense of the term) is important for evaluating the effectiveness of treatment methods and prognosis of disease outcome. These include among these parameters special place is the quality of life. The term, recently born in Western philosophy, has already taken a significant place in sociology and medicine (Novikov GA et al Prospects for the development and improvement of palliative care to cancer patients in Russia // Russian Medical Journal, 1995, №1, -. C. 13-17; Merabishvili VM Malignancies in St. Petersburg in 1996 - St. Petersburg, 1999. - 219 p .; Chissov VI, Novikov GA, Prokhorov BM Palliative care -. one of the directions of the domestic oncology prioretetnye // III Congress "Palliative medicine and rehabilitation in health care" Palliative medicine and rehabilitation, 2000, №1-2, -. C.6).

The severity of the condition inoperable cancer patients and consequently poor quality of life is often caused by impaired patency of the central bronchi and trachea, and then raises the question of the need to increase the recanalization of the respiratory surface, the elimination of the phenomena of obstructive pneumonia and be able to conduct anti-tumor treatment, prevent or delay relapse. Is urgent and proactive impact on the tumor preventing bronchus obturation (GA Novikov, VV et al Starinskiy development prospects in Russia palliative care to cancer patients // Topical Issues of Oncology:. Mater between Sympos, 1996, St. Petersburg.. ., May 14-17, 1996 s.215-216; Asahina SM, Zolotcov AG, et al radiation reactions and complications of palliative radiotherapy of lung cancer patients // IV Conference "palliative care in. Oncology ", April 1999, Antalya, Palliative medicine and rehabilitation, №3, 1999, p.35; Trachtenberg AH, Chissov VI Clinical onkopulmonologiya // Moscow - 2000. - 599 s)... The results of the application of this group of patients chemoradiotherapy remains unsatisfactory. Efforts to improve immediate results of treatment through improved remote radiation exposure options proved ineffective, as the increase in the dose level of tolerance load is limited to surrounding healthy tissue and organs. In these circumstances, there are obvious advantages intracavitary (contact) exposure, providing much greater focal dose in the tumor than in adjacent tissues. With the introduction into clinical practice of modern devices for brachytherapy with a walking source of radiation are associated certain hopes to increase the effectiveness of palliative care. The contingent of patients, which may be subjected to an intracavitary radiation therapy is limited, due to occlusion, or a sharp narrowing of the lumen of the central bronchi, or trachea, making it impossible to deliver an applicator with a radioactive source to the tumor (AH Trachtenberg Lung cancer -. M .: Medicine . - 1987. - 304 p .; Cox JD, Byhardt RW, Komaki R. the Role of Radiotherapy in Squamous, Large Cell and adenocarcinoma of the lung // Seminars Oncol -. 1983 - Vol.1 -. P.81-94 ; Sorensen JB Prognosis and prognostic factors in adenocarcinoma of the lung. / / Dan. Med. Bull. - 1992. - Vol.5. - P.453-463; Feldman ER, Eagan RT, Schaid DJ. Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis // Mayo Clinic Proc - 1992. - Vol.67 - P.27-32)..... Analysis of published data showed the novelty of "a method of treating locally advanced cancers of the central bronchi and / or trachea."

The closest to the proposed method is a method combining laser recanalization of the lumen airway proposed previously with photodynamic therapy (Sokolov VV Filonenko EV, DG Sukhin Prolonged photodynamic therapy of incurable cancer patients // V Conference "Palliative care in Oncology ", April 2001, Bodrum, Palliative medicine and rehabilitation, No 2-3, 2001 - p.25; Stranadko EF, Filkova EM Meshkov VM The new version of photodynamic therapy for locally advanced malignancies // New technologies in clinical practice:. Collection of scientific papers based on scientific and practical conference dedicated to the 85th anniversary of the Central clinical hospital named after Semashko, Moscow, 1999. - M., 1999. - S.70-72; Zaporozhan VN Grubnik VV, Poddubny BK Lasers in endoscopy Odessa: Medical State University, 1997. - 220)... The advantages of these techniques are added to the effects of argon plasma electrocautery, brachytherapy and external beam radiotherapy, but also features pharmacodynamics of new effective photosensitizer "photodithazine" used during photodynamic therapy, to obtain the maximum cytoreduction and optimal recovery of the tracheal lumen and / or bronchus prior to radiation therapy.

The technical result of the method is 1) a reduction in tumor mass (cytoreduction), 2), airway, 3) intoxication and decrease pain. This is achieved by carrying out argon plasma recanalization of the trachea and / or bronchi (the device ERBE APC-300, registration number 98/1735 on 28/12/98. Certificate №4418755) followed by photodynamic therapy, and then performing brachytherapy and external beam radiotherapy.

The clinic Institute of Oncology named after prof. NN Petrov used functional complex consisting of a control unit argonopitaniem, a high-frequency generator and a flexible probe electrodes. In the complex there was a functional software with the ability to select the optimal parameters of the power generator and argon flow, allowing accurate control of the depth and extent of the impact. Argon plasma coagulation of - a method of high-frequency monopolar electrosurgery in which the high frequency current energy is transferred to the cloth in a contactless manner by means of ionized argon. Argon plasma arc is formed between the electrode and the tissue section having the least resistance. The resultant dehydration (desiccation) of coagulated tissue increases its resistance, which leads to the displacement of argon arc on the tissue site with less resistance, ensuring the homogeneity and the controllability of the coagulation zone depth effects. coagulation in depth according to the power application electrode and the length is less than 3 mm, reducing the risk of perforation. Typically, coagulation was carried out at 60-90 watts of power (70 W average) at an argon flow rate of 2.0-2.4 liters / minute (average of 2.2 l / min). One advantage of this method is coagulation in an oxygen-free environment, allowing work on the fabric without significantly its carbonization (carbonization).

For the photodynamic therapy was used photosensitizer "photodithazine" (registration number 249188) on the basis of a water-soluble form of chlorine E6, which has a number of biological, physical, chemical and energy characteristics, distinguishes it from previously used in clinical photosensitizers, such as: 1) a strong absorption band wavelength in the red region of the spectrum (662 nm); 2) rapid pharmacodynamics (time accumulation in the tumor - 2 hours, while the total elimination from the body - 24-36 hours); 3) high amphiphilicity (coefficient accumulation in tumors compared to normal tissue 10: 1-15: 1); 4) low dark phototoxicity, providing ease of use in clinical and outpatient settings; 5) high luminous photocytotoxicity associated with the active generation of singlet oxygen (75-96%) in the interaction with the laser radiation; 6) high penetration into the tissue, as the laser wavelength is in the range of optical clarity; 7) A large therapeutic range of the drug; 8) low allergenicity. Irradiation was carried poluprovodnikovm laser "Atkus-2" (registration number 29/05010104 / 5958-04 MoH from 26.01.04, certificate of conformity RU.IM 15.V.00404 ROS) with a power density of 300 mW / cm 2; total radiation power -. 400 J. The dose ranged from 0.8 to 1.5 mg / kg body weight. The irradiation of the tumor was performed 2 hours after administration of the drug. Also wear sunglasses during the day no other protective measures are not required. Introduction Photoditazin followed by laser irradiation did not cause widespread phototoxic endotraheobronhita. Hyperemia mucosa observed at a fairly limited area, adjacent to the "exposure zone". In neither case were observed cumulative effect.

Intraluminal brachytherapy was performed on the unit Mikroselektron HDR (Nucleotron) with a source of iridium-192 high dose rate with activity 5-10 curies. source movement is carried out in steps of 5 mm. The length of the path of movement of the source of 5 to 20 cm, depth 10 mm isodose reference to the source. For endokyuriterapii unused standard applicator placed under local anesthetic through the instrument channel fibreoptic so as to provide movement of the source by a distance comprising a tumor or a wall of the bronchus and trachea above and below the tumor from 1 to 3 cm. During the irradiation were carried principles conformal radiotherapy aimed which is summing up the maximum possible radiation dose to the tumor and reducing the dose level of load in the area adjacent organs and tissues, thereby reducing the frequency of radiation damage in the treatment of primary tumors. External beam radiotherapy was performed on LUEV-15M1 apparatus to SOD 45-55 Gy.

The study included data on 15 patients, which from April 2001 to June 2003 in our clinic produced a total of 23 sessions argon plasma electrocoagulation followed by brachytherapy and external beam radiotherapy. In 7 patients had a tumor lesion of one of the equity of the bronchi with the transition to the main, and 4 - the defeat of the main bronchi with the transition to the trachea and 4 defeat of one of the equity of the bronchi. The morphological structure of the tumor was as follows: 9 patients set squamous cell carcinoma, in 6 - adenocarcinoma.

Complete recanalization was achieved in 10 (66.7%) patients and partial in 5 (33.3%) - with a significant peribronchial or peritrahealnom components. In all patients, the intervention was performed for palliation. Immediately after recanalization patients reported subjective improvement in well-being, and that was confirmed by objective data - physical examination, the improvement of indicators of clinical, biochemical and blood gas analyzes, radiographic data.

Brachytherapy as the 2nd phase of treatment was carried out in the period from 1 to 3 weeks after recanalization. This is the time needed to process the reactive inflammation subsided, escharotomies and rejection of necrotic parts of the tumor. Summing up the dose from 14 to 28 Gy in Mode 1 once a week for 7 Gy.

External beam therapy is the 3rd stage of the treatment was carried out immediately after brachytherapy mode 5 times a week for up to 1-2 Gy SOD 45-50

Of the 15 patients treated up to 12 months need to be re-argon plasma recanalization did not have a single patient, and in a period of 12 to 18 months - in 4 patients. From the generalization of the process to date, 6 patients died. At the dispensary observation remain the 9 patients.

Inventive step of the proposed method is confirmed by the fact that in all cases fully (66.7%) or partially (33.3%) restored patency of the bronchi and trachea, marked improvement in respiratory function, reducing intoxication and pain syndrome. The mean duration of disease-free period with complete clinical remission was 28 months (12-33 months), and in partial remission - 15 months (8 to 23 months), whereas the duration of the laser recanalization relapse-free period is on average 11 months, with a standard high-frequency electrocoagulation - 9 months, and during chemoradiotherapy - 7 months.

As clinical studies and to confirm the terms "industrial applicability" present the following clinical observations.

example 1
P.M.V. patient, 39 years old. Complaints on admission to the rise in temperature to 39-40 ° C; dyspnea at moderate exertion, weakness, cough with purulent sputum. Clinical diagnosis: cancer of the right upper lobe bronchus with the transition to the main and trachea. A morphological study (bronhobiopsiya) - squamous cell carcinoma. 12.03.2001 Operation of argon-plasma coagulation of the tumor reached a partial recanalization. Duration of surgery - 25 minutes. 22 and 29.03.2001, the - two sessions of photodynamic therapy (photodithazine - 1.5 mg / kg; total radiation power - 400 J at a power density of 300 mW / cm 2). 12 and 29.04.2001, the brachytherapy to ODS 14 Gy. External beam radiotherapy of 07.05.2001 - 03.06.2001 of up ODS 48 Gy. In the dynamic clinical, radiological and endoscopic observation of remission 17 months.

example 2
G.SH.P. patient, 72 years old. Complaints on admission of shortness of breath with little exertion, weakness, raising the temperature to 38-39 ° C, hemoptysis. Clinical diagnosis: cancer of the right lobar bronchus with the transition to verhnedolevoy and CEO. A morphological study (bronhobiopsiya) - high-grade adenocarcinoma. 22.02.2002 Operation of argon-plasma coagulation of the tumor reached a partial recanalization. Duration of the operation 10 minutes. 17/03/2002, the - session of photodynamic therapy (photodithazine - 1.5 mg / kg; total radiation power - 400 J at a power density of 300 mW / cm 2). 13.04-20.05.2002 of brachytherapy to the ODS 21 Gy. External beam radiotherapy of 25.05.2002 - 10.07.2002 to 45 Gy. In the dynamic clinical, radiological and endoscopic observation of partial remission 9 months (for the moment).

example 3
D.S.L. patient, 58 years old. Complaints on admission of shortness of breath with little exertion, weakness, fever up to 38 ° C, hemoptysis. Clinical diagnosis: cancer of the left main bronchus with metastases in the lymph nodes of the mediastinum. A morphological study (bronhobiopsiya) - adenocarcinoma. 28.06.2003 Operation of argon plasma coagulation of the tumor, achieved complete recanalization. Duration of surgery - 35 minutes. 15.07.2003 - two sessions of photodynamic therapy (photodithazine - 1.0 mg / kg; total radiation power - 400 J at a power density of 300 mW / cm 2). 07-30.07.2003 of brachytherapy to the ODS 21 Gy. External beam radiotherapy of 12.08.2003 - 17.09.2003 to 50 Gy. In the dynamic clinical, radiological and endoscopic observation of complete remission 12 months.

CLAIM

A method of combined treatment of locally advanced malignant tumors of the trachea and / or bronchi, comprising carrying out argon plasma recanalization of the lumen of the trachea and / or bronchi, with a power of 60-90 watts, followed by brachytherapy source in path length 5-20cm movement step of 5 mm and a depth reference isodose 10 mm from the source; motion applicator secured above and below the tumor from 1 to 3 cm and summing the dose of 14 Gy to 28 Gy in mode 1 time per week to 7 Gy; and teletherapy mode five times a week for up to 1.2 Gy dose of 45-55 Gy SOD, characterized in that additionally, before the start of radiation therapy with photodynamic therapy is conducted drug "photodithazine" 0.8-1.5 mg / kg, and the radiation of a semiconductor laser wavelength of 662 nm and a total energy dose of 400 J.

print version
Publication date 06.01.2007gg