Method of treating stage iia hodgkin's lymphoma

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology and radiology, and may be used for treating stage IIA Hodgkin's lymphoma. That is ensured by 3-4 therapeutic courses of chemotherapy by the scheme ABVD - adriablastine, bleomycine, vinblastine, dacarbazine. It is followed by chemotherapy by the scheme AVB - adriablastine, vinblastine, dacarbazine. From the 2nd day of the AVD course, the radiation therapy covering initially involved zones is applied at single basic dose 1.2 Gy, daily 2 times a day every 4 hours. If the initial tumour lesion is less than 5 cm, the radiation therapy is applied to total basic dose 30 Gy, while the lesions more than 5 cm requiring dose up to 36 Gy.

EFFECT: method provides reducing total treatment length at least by 2 months, reducing a risk of recurrences, reducing a probability of secondary tumours and late complications of the radiation therapy ensured by the intensified combined chemoradiation treatment.

2 ex

 

The invention relates to medicine, more specifically to Oncology and radiology, and may find application in the treatment of lymphoma.

Incidence rates of Hodgkin lymphoma (HL) do not exceed 2-4 cases per 100,000 people per year. Hodgkin lymphoma accounts for approximately 30% of the total number of malignant lymphomas. Mortality from LH from the late 90's to early 2000s decreased by 60% in Western Europe and America, amounting to 0.5 per 100,000 in men and 0.3 per 100,000 in women.

In accordance with the classification of Ann arbor to stage II LH include clinical variants of the disease, in which affected two or more lymph area on one side of the diaphragm or localized lesion of one extralymphatic organ/tissue lesion with regional lymph nodes and other lymph nodes on the same side of the diaphragm. In 97% of cases, affected lymph collectors above the diaphragm. The sub-phases And include patients without specific symptoms of intoxication. When there is unexplained loss of weight >10% for 6 months of unexplained by other causes long-term (not less than two weeks) increase in body temperature above 38,0°C, profuse night sweats, set the substage, MIS C.

The main method of treatment of patients with HL is chemoradiotherapy. Therapeutic win this combin, the tion is to reduce the frequency of relapses (average, 20%), developing when conducting in patients with LH I-II stage-only radiotherapy and in patients with III-IV stages - only chemotherapy.

According to the summarized data of the literature, five-year survival of patients in the early stages of the disease (I-II (A) is 90%. This highlights LH from a number of other lymphoproliferative disorders. The increased life expectancy of patients with HL have revealed new problems: the vast majority of studies show that overall survival was significantly lower survival, disease-specific. This observation is due, first and foremost, the development of second tumors and death in complete remission patients from late complications.

After analyzing studies on different approaches to therapy LH IIA stage without risk factors, the majority of authors recommend performing the radiation treatment volume Subtotal/total nodal irradiation enhanced fields to the total focal dose (SOD) 30-36 Gy or 4-6 cycles of chemotherapy and radiation affected areas to SOD 20-36 Gy. Usually the patient is first courses of chemotherapy, and then, not earlier than one month, perform radiation therapy.

In the ongoing search for optimal therapy programs to patients LH IIA stage in which adequate total focal dose of l is the U.S. treatment will improve outcomes and quality of life of patients, reducing the frequency and severity of complications. The present invention relates to the treatment of this stage HL.

In MCRT since 1999 with radiotherapy and chemoradiation treatment of patients with primary LH method modified multifractional dose at which radiation therapy is carried out in a single focal dose (ROD) 1.2 G, 2 times a day with intervals of 4 hours, up to SOD 30-36 Gy (patent No. 2191049 from 20.10.2002). Were shown such important advantages of this mode of radiation therapy, as reducing the severity and frequency of radiation lung damage. Since 2003 this mode is used after chemotherapy courses during irradiation of the affected areas.

The term "affected area" means the division of functional lymphatic regions (Ann. Oncol. - 2002. - V.13 (11). - R-83). For LH IIA stage with lymph collectors above the diaphragm is: 1) cervical (left and right), including cervical, supraclavicular and infraclavicular lymph nodes; 2) the mediastinum (1 region), including the lymph nodes of the roots of the lungs on both sides; 3) axillary (left and right), including the axillary, supraclavicular and infraclavicular lymph nodes. The decrease in the volume of LT under irradiation of only the affected areas does not reduce the direct results of combined treatment of HL compared using the Subtotal/total n is yuandong irradiation, but it contributes to the reduction in the incidence of early and late complications of radiation therapy and second tumors.

Closest to the proposed method is described in the publication N.V. Ilyina et al. Radiation and combined treatment of patients with Hodgkin's lymphoma stage II (Oncology Issues. - 2010. - T. No. .5. - S.623-625). This publication summarized the experience in treatment of 179 patients with stage II LH. Patients were divided into groups receiving different treatment protocols, the most optimal from the point of view of the authors, was the method of treatment, which included chemotherapy and radiation is primary affected areas, taken as a prototype.

According to the prototype of patients with a diagnosis of LH IIA stage of treatment begins with chemotherapy scheme ABVD (adriablastin, bleomycin, vinblastine, dacarbazine in the 1st and 14th days intravenous). Patients undergo 3-4 cycles of chemotherapy according to this scheme, and one month after completion of chemotherapy courses conducted radiation therapy for primary affected area. Field irradiation is formed individually for each patient, based on the method of exposure through extensive field complex configuration including initial spread of the disease. Radiation therapy is carried out in a single focal dose of 1.2 Gy to the main point of every day 2 times a day with what tervalon 4 hours. Irradiation is carried out on the linear accelerators SL 75-5 boundary energy bremsstrahlung 6 MeV. Total dose on the primary-affected zone when after chemotherapy residual tumors are 36 Gr, in their absence - 30 Gr.

In the prototype method is described for stage II LH does not say how many patients in this group were with stage IIA (probably the majority), because according to the description of the treatment for the specialist it is obvious that patients with II stage in this study was negligible quantity (modern protocols of their treatment suggest a greater contribution of chemotherapy and in some cases do not involve radiation therapy at all).

This method allows to reduce the number of relapses and the number of hematological complications of treatment. The disadvantages of this method is the duration of treatment (not less than 5 months), the authors were unable to completely solve the problem of disease recurrence, including in the field of irradiation. In addition, this method of treatment does not take into account the size of primary lesion. At the present stage it seems to us unwarranted conclusions dose of 30 Gy for patients who have achieved complete regression of lymph nodes, but when the primary staging had a large tumor (>5 cm), as this may cause recurrence of the disease.

The technical result of the present invention is to reduce the total time of treatment of the patient, reducing the risk of relapse due to the intensification of joint treatment chemoradiation treatment.

This technical result is achieved by the fact that in the known method of treatment for Hodgkin's lymphoma stage IIA with the lymph nodes above the diaphragm, including 3-4 cycles of chemotherapy according to the scheme ABVD (adriablastin, bleomycin, vinblastine, dacarbazine) and radiation therapy in the initially affected area with a single focal dose of 1.2 G daily 2 times a day with an interval between sessions of 4 hours, according to the invention the last cycle of chemotherapy perform under the scheme AVD (adriablastin, vinblastine, dacarbazine), and radiation therapy starting from the 2nd day of chemotherapy when the size of the primary lesion less than 5 cm to the total focal dose of 30 Gy, and when the lesions more than 5 cm to 36 Gy.

The background to the invention this method appeared to our many years of experience treating patients with Hodgkin's lymphoma and clinical situation with which we are faced. We received a patient with Hodgkin's lymphoma stage IIA with lesions of the mediastinum. The patient developed symptoms of compression of the upper Vena cava, he started chemotherapy scheme ABVD, but on the 3rd day after injection improvements, patientsubject severe shortness of breath, increased facial swelling and cyanosis. Due to progressive deterioration of the patient, contrary to common methods of treatment of HL (continued chemotherapy within 14 days), we decided on the background of chemotherapy to attach radiation therapy to the affected region, namely in the mediastinum with a single focal dose of 1.2 G daily 2 times a day with an interval between sessions of 4 hours. We had planned to bring the total focal dose of not more than 20 Grams, because naturally feared the development of severe hematological complications. During the treatment the patient's condition began to improve. To our surprise, by the time of deciding the dose of 19.2 G there were no hematological complications. In this regard, we continued with the planned introduction of drugs of chemotherapy and at the same time continued the mediastinal irradiation to a total dose of 36 Gy. This helped to arrest syndrome compression of the upper Vena cava. Subsequently the patient had another 4 cycles of chemotherapy. Achieved clinical remission. Late complications of treatment was not.

Based on this clinical experience, we have developed the proposed method of treatment for Hodgkin's lymphoma stage IIA, which accumulated after the positive results of treatment of patients and presents us as the present invention.

Holding lucev the th therapy the day after the start of the last cycle of chemotherapy reduces the duration of treatment at least 2 months in addition, the combination of chemotherapy and radiation therapy enhances the effect, which reduces the risk of true (local) recurrence. In addition, this combination, as we have shown, provides for prevention of late complications of radiation therapy and second tumors, because it allows to reduce the dose as radiation therapy (traditionally supplied dose 36-44 Gr), and to exclude from the last cycle of chemotherapy polymethoxy drug "Bleomycin".

It turned out that the exception from the last cycle of chemotherapy drug Bleomycin not only worsened the results of the treatment, but contributed to the prevention of such late complications of treatment as pulmonary.

Radiation therapy in the complete regression of lesions smaller than 5 cm after chemotherapy to a total dose of 30 Gy and 36 Gy in patients with large (>5 cm) centers of disease at initial staging provides full local control and is necessary and sufficient.

The method of treatment is as follows.

The patient with a diagnosis of Hodgkin lymphoma stage IIA treatment begins with chemotherapy scheme ABVD (adriablastin, bleomycin, vinblastine, dacarbazine). Is 3-4 cycles of chemotherapy according to this scheme. With full recourse previously increase the local lymph nodes last chemotherapy perform under the scheme AVD (adriablastin, vinblastine, dacarbazine). Radiation therapy is started from the 2nd day of chemotherapy. Field exposure at the same time necessarily form individually for each patient, based on the method of exposure through extensive field complex configuration including initial spread of the disease. Irradiation is carried out via the front-rear extended field of complex configuration on linear accelerators SL 75-5 boundary energy bremsstrahlung 6 MeV. Radiation therapy is carried out in a single focal dose of 1.2 G of basic accounting points 2 times a day with an interval of 4 hours. Radiation therapy for lesions less than 5 cm at initial staging spend up to the total focal dose of 30 Gy, when the lesions more than 5 cm to 36 Gy.

The essence of the method is illustrated by the following examples.

Example 1.

Patient T., 1983 birth, medical history, No. 3465, hospitalized in MCRT 21.09.2009 with complaints about the increase in cervical lymph nodes on the left.

From history - in the summer of 2009, after acute respiratory infections noted the increase in cervical lymph node. In August 2009 in the city Oncology center of Saint-Petersburg was held this node biopsy, the histological conclusion: Hodgkin lymphoma, nodular sclerosis.

Upon receipt: satisfactory condition, the Constitution normostenichesky, growth 165 is m, weight 54 kg Skin clean, Zev - without a pathology, bone and joint apparatus is normal. Increased to 1.5 cm cervical lymph nodes on the left. The thyroid gland is not enlarged, no edema. Borders of the heart is within normal limits, heart rate (HR) 86 min, heart sounds clean, rhythmic. Chest right shape, symmetrically involved in breathing, breathing hard, no wheezing. The abdomen is soft, painless, liver at the edge of the costal arch, the spleen is not enlarged. The kidneys are not palpable. The Karnofsky index 90.

According to the survey:

Ultrasonography (ultrasound): the neck on the left are defined 2 hypoechoic lymph node, 2 cm in diameter and 1.5 cm abdominal Organs without pathology.

Computed tomography of the chest: lymphadenopathy mediastinal nodes from 1.5 to 2 cm

Diagnosis: Hodgkin's Lymphoma, nodular sclerosis, clinical stage IIA (08.2009). The defeat of the cervical lymph nodes and mediastinal.

With 28.09.2009 started chemotherapy scheme ABVD (adriablastin 45 mg, bleomycin 15 mg, vinblastine 10 mg, dacarbazine 650 mg intravenously in the 1st and 14th days of course). Satisfactorily, noted a positive trend in the reduction of affected lymph nodes. With 12.10.2009 had a second course of therapy according to the same scheme. Satisfactorily. Showed complete regression of cervical limfaticheskie the nodes and mediastinal lymph nodes. Discharged on 28.12.2009 break in treatment.

Following hospitalization with 09.11.2009. Complaints at admission was not charged. The condition is satisfactory. The skin is clean, Zev - without a pathology, bone and joint apparatus is normal. Peripheral lymph nodes are not enlarged. The thyroid gland is not enlarged, no edema. Borders of the heart is within normal limits, heart rate 76 min, heart sounds clean, rhythmic. Chest right shape, symmetrically involved in breathing, breathing hard, no wheezing. The abdomen is soft, painless, liver at the edge of the costal arch, the spleen is not enlarged. The kidneys are not palpable. The Karnofsky index of 100.

According to the control ultrasound, complete regression of the previously enlarged cervical lymph nodes. According to the CT scan showed complete regression of mediastinal lymph nodes.

With 16.11.2009 in connection with the positive dynamics of the disease and complete regression of lymph nodes started chemotherapy scheme AVD (adriablastin 45 mg, vinblastine 10 mg, dacarbazine 650 mg intravenously in the 1st and 14th days of course). On the second day of chemotherapy 17.11.2009 was started radiation therapy for primary affected area (cervical lymph nodes on the left and mediastinum) mode multifractional with a single focal dose of 1.2 G daily 2 times a day with an interval between sessions of 4 hours to a total dose of 30 Gy. Les is giving satisfactorily. Hematological complications during treatment were observed. The patient was discharged in satisfactory condition 23.12.2009.

For outpatient examination 18.02.2010 showed complete clinical remission, the late complications of treatment were not identified. The patient is observed for the present time, is maintained clinical remission.

Example 2.

Patient S., born in 1978, case history No. 3593 hospitalized in MCRT 12.11.2009 with complaints about the increase in cervical lymph nodes.

From history - in September 2009, noted the increase in the submandibular lymph node on the right. 16.10.2009 in city hospital No. 2 Saint-Petersburg was held deleting this node, the histological conclusion: Hodgkin's lymphoma, mixed-cell option.

Upon receipt: satisfactory condition, the Constitution giperstenichesky, height-178 cm, weight 108 kg Skin clean, Zev - without a pathology, bone and joint apparatus is normal. Increased to 2 cm submandibular lymph nodes, up to 1.5 cm - cervical lymph nodes. The thyroid gland is not enlarged, no edema. Borders of the heart is within normal limits, heart rate 76 min, heart sounds clean, rhythmic. Chest right shape, symmetrically involved in breathing, breathing hard, no wheezing. The abdomen is soft, painless, liver at the edge of the costal arch, the spleen is not enlarged. The kidneys are not palpable. the index Karnofsky 90.

Survey data:

Ultrasound: the conglomerate hypoechoic lymph nodes in the neck right 51×21 mm (>5 cm) and 24×13 mm, left - 24×13 mm, in the left submandibular region - 12×10 mm abdominal Organs without pathology. Positron emission tomography of the whole body with 18-Tordesillas: a lesion of the cervical and submandibular lymph nodes on the right.

Diagnosis: Hodgkin's Lymphoma, mixed-cell variant, clinical stage IIA (10.2009). The defeat of the cervical and submandibular lymph nodes on both sides.

With 24.11.2009 started chemotherapy scheme ABVD (adriablastin 50 mg, bleomycin 15 mg, vinblastine 10 mg, dacarbazine 700 mg intravenously in the 1st and 14th days of course). Satisfactorily. With 22.12.2009 had a second course of therapy according to the same scheme. Satisfactorily. The positive effect of regression of peripheral lymph nodes. Discharged on 29.12.2009 break in treatment.

Following hospitalization with 11.01.2010, case history No. 208. Complaints upon receipt does not show. The condition is satisfactory, the Constitution giperstenichesky, height-178 cm, weight 105 kg Skin clean, Zev - without a pathology, bone and joint apparatus is normal. Peripheral lymph nodes are not enlarged. The thyroid gland is not enlarged, no edema. Borders of the heart is within normal limits, heart rate 76 min, heart sounds clean, rhythmic. Chest to etka correct form, symmetrically involved in breathing, breathing hard, no wheezing. The abdomen is soft, painless, liver at the edge of the costal arch, the spleen is not enlarged. The kidneys are not palpable. The Karnofsky index 90.

According to the control ultrasound of the neck on the right is saved increased to 23×10 mm and 22×15 mm two lymph node, other previously enlarged lymph nodes are not defined.

Due to the presence of incomplete regression of lymph nodes with 25.01.2010 started the third cycle of chemotherapy under the scheme ABVD. Satisfactorily.

According to the U.S. from 06.02.2010, showed complete regression of the previously enlarged cervical lymph nodes. In this regard, 08.02.2010 started chemotherapy scheme AVD (adriablastin 50 mg, vinblastine 10 mg, dacarbazine 700 mg intravenously in the 1st and 14th days of course). From the second day of chemotherapy (09.02.2010) was started radiation therapy for primary affected area (cervical and submandibular lymph nodes on both sides) mode multifractional with a single focal dose of 1.2 G daily 2 times a day with an interval between sessions of 4 hours to a total dose to the cervical lymph nodes on the right - 36 Gy (because at the initial examination showed lesions more than 5 cm), submandibular lymph nodes on both sides and cervical lymph nodes on the left up to a total dose of 30 Gy (as in primary staging they were less than 5 cm).

Treatment satisfactorily.

In the clinical analysis of blood at discharge 10.03.2010: leukocytes of 6.71*109/l, hemoglobin 150 g/l, erythrocytes 5,18*1012/l, platelets 253*109/HP

In subsequent outpatient examination 12.04.2010 showed complete clinical remission, late complications of radiation therapy is not revealed. The patient has to present, is maintained clinical remission.

To date, the proposed method were treated 12 patients IIA stage Hodgkin's lymphoma. In all patients the treatment was carried out without late complications, achieved clinical remission. The observation period for patients ranges from 1.5 to 2.5 years, all patients were in complete clinical remission and continue to occur.

The proposed method of treatment in comparison with known has advantages.

1) reducing the overall treatment time of at least 2 months (3-4 months with the proposed method, while the treatment method prototype takes 5-6 months).

2) reducing the risk of true recurrence - single patient was found to relapse.

3) Reduction in the probability of developing second tumors and late complications of radiation therapy, we observed a delayed complications of a single patient, while in the treatment method prototype they were observed. The proposed method Les the program developed in the Department of radiation therapy systemic diseases and radiation pathology UHF MCRT and was clinically tested in the treatment of 12 patients with a positive result.

The method of treatment of Hodgkin lymphoma stage IIA with the lymph nodes above the diaphragm, including 3-4 cycles of chemotherapy according to the scheme ABVD (adriablastin, bleomycin, vinblastine, dacarbazine) and radiation therapy in the initially affected area with a single focal dose of 1.2 G daily 2 times a day with an interval between sessions 4 h, characterized in that the last cycle of chemotherapy perform under the scheme AVD (adriablastin, vinblastine, dacarbazine), and radiation therapy starting from the 2nd day of chemotherapy when the size of the primary lesion less than 5 cm to the total focal dose 30 G, and when the lesions more than 5 cm to 36 Gy.



 

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2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology, and aims at combination treatment of locally advanced rectal cancer. It involves radiation therapy with underlying introduction of capecitabine 825 mg/m2 times a day on the radiation days. The treatment is two-staged: the fist stage involves gamma-ray teletherapy in a standard fractionation mode at single basic dose 2.0 Gy for 5 days a week to total basic dose 40.0 Gy. At the second stage, the interval of 14 days is followed by 5 sessions of intracavitary gamma-ray therapy at single basic dose 3.0 Gy to total basic dose 16 isoGy.

EFFECT: method provides higher clinical effectiveness in locally advanced rectal cancer ensured by higher radiation dose directly covering the tumour and reduced radiation dose on healthy organs and tissues.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to oncology, and may be applied in treating locally advanced breast cancer with tumour skin ulceration. That is ensured by CMF chemotherapy, 5-fluorouracil chemotherapy in the form of Koletex-5-fluor tissue applications and radiation therapy. The Koletex-5-fluor tissues are applied on the ulcer centre daily 2-3 times a day and changed every 2 days. The radiation therapy is performed in a mode of average dose fractionation on an area of a breast base and an area of regional lymph outflow. Herewith, 5-7 days before the radiation therapy, the ulcer area and the whole breast are coated with a thin layer of the 'Hydrogel Coletex-Phyto Tissue' material 3 times a day. Additionally, the ulcer area is coated with the 'Coletex-Phyto' textile tissues above the hydrogel material. The radiation directly covers the tissue and hydrogel. The ulcer borders are treated with the 'Hydrogel Coletex-Phyto Tissue' material 2-3 times a day for the whole period of radiation. After the termination of the radiation therapy, the ulcer centre is coated with the 'Coletex-Phyto' textile tissues, while the ulcer borders are treated with the 'Hydrogel Coletex-Phyto Tissue' material for 1-2 weeks.

EFFECT: implementing the method provides higher clinical effectiveness ensured by faster healing of tumour ulcers, reduced drug load, lower toxicity and enabled continuous radiation therapy.

1 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. A therapeutic system comprises an imaging device, a therapy planning unit, a therapeutic device. The therapy planning unit comprises a therapy prescription unit which calculated the required therapy to be applied in a patient or any other object. The therapy prescription system uses a pathology model and a history of biological values specific for the patient for purposes of optimising the applied therapy.

EFFECT: use of the given group of inventions enables adapting the therapy plan with taking into consideration the biological variations regarding a specific pathology or a patient.

43 cl, 6 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and can be used for combination treatment of the patients suffering eyelid malignancies. A method involves local radiomodification by peritumoral introduction of Methotrexate 10 mg pre-incubated in autoplasma 10 ml at t=37°C for 30 minutes preceded by subbulbar introduction of diprospan 1 ml. One hour later, the radiomodification is followed by neoadjuvant radiation therapy at depth 0.5 cm by basic dose 20 Gy, and no more than 24 hours after the radiation, a surgical operation is performed.

EFFECT: method provides intensified radicality of the tumour exposure, higher surgical ablasticity, lower risk of cancer dissemination, maximally maintained reparation ability and functions of normal ocular tissues, minimised therapeutic complications, reduced length of treatment.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology and deals with method of treatment in case of urinary bladder cancer. Combined treatment with application of neoadjuvant system polychemical therapy by the following scheme: 1 day -5-fluoruracyl, 2 day - cyclophosphane+vinblastine, 14 day - methotrexate, 15 day - doxorubicin, 16 day -cisplatin, and adjuvant intrabladder chemical therapy with preparation doxorubicin during 2 years, on the first day after operation doxorubicin 40 mg is instilled, then 4 instillations of doxorubicin in dose 40 mg with 7 day interval, then doxorubicin 40 mg is instilled with 30 day interval during 11 months, after that during the second year instillations of doxorubicin in dose 20 mg are performed after 1 month.

EFFECT: invention ensures improvement of results of organ-preserving treatment by reduction of number of urinary bladder cancer recurrences.

1 ex

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