RU2286818C2 - Method for treating local relapses of mammary cancer - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: one should carry out radiation therapy with quick neutrons 6.3 Mev twice weekly in two stages: at the first stage it is necessary to prescribe 3-4 seances of neutron therapy at interval of 48-72 h directly onto area of tumoral relapse and onto surrounding normal tissues at the distance of about 3-5 cm against tumoral foci, single focal dosage being 1.6-2.0 Gy, relative biological efficiency corresponds to 2.91-2.79, onto the skin - 2.0-2.2 Gy, up to total focal dosage being 6.6±1.5 Gy, onto the skin - 8.3±1.3 Gy, at the second stage it is necessary to carry out gamma- or electronic therapy at single focal dosage being 2.0-3.0 Gy, 5 fractions weekly, moreover, total course dosage of neutron-photon irradiation per a focus corresponds to 60 Gy by isoeffect at duration of irradiation course of about 20-25 d.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to oncology, and can be used in the treatment of local relapses of breast cancer (breast cancer) after a combined or complex treatment with radical mastectomy.

Known methods for treating local recurrences of breast cancer with photon therapy with a fast electron beam of 6-22 MeV energy or 1.25 MeV gamma-ray therapy for the area of relapse of the same half of the anterior chest wall and the region of regional lymph outflow to a total focal dose (SOD) of 44-50 Gy with a subsequent reduction in the volume of irradiated tissue to local and summing up radiation therapy to SOD 56-80 Gy [1].

The disadvantages of these methods are:

- a large amount of tissue of the anterior chest, subject to radiation therapy, which causes a large radiation load on the patient's body and can lead to radiation reactions and damage to normal tissues;

- the frequency of local cure for local recurrence of breast cancer is 71.5 ± 8.4% when using the value of the total focal dose in the range of 50-80 Gy;

- the development of radioresistance of local relapses to photon radiation therapy in the event of a re-tumor.

The closest way to treat local relapses of breast cancer for a positive effect is the method of radiation therapy with fast neutrons of 6.3 MeV single focal dose of 1.2-1.4 Gy (RBE - 3.2-3.0), 2 times a week, 6-8 sessions, up to the total focal dose (SOD) of fast neutrons - 11-12 Gy, which corresponds to 46-50 Gy according to the isoeffect, for 4-5 weeks. In this case, the complete regression of local relapses reached 100% [2] (prototype).

The disadvantage of this method is:

- carrying out radiation therapy with fast neutrons of 6.3 MeV takes a long time from 4 to 5 weeks (28-35 days);

- neutron therapy in its own version causes pronounced side effects in the form of local radiation reactions of irradiated skin areas (2-3 severity) and radiation damage to normal tissue in the irradiation sites in more than 57% of patients.

The objective of the present invention is to reduce the duration of radiation therapy and reduce the number of side effects - local radiation reactions of the skin and radiation damage to normal tissue at the site of exposure.

The specified task in the proposed method is achieved in that the treatment is carried out in two stages: at the first stage, 3-4 sessions of radiation therapy with fast neutrons of 6.3 MeV are prescribed, with an interval of 48-72 hours, directly to the area of tumor recurrence and surrounding normal tissue at a distance at least 3-5 cm in different directions from the tumor foci, with a single focal dose (ROD) - 1.6-2.0 Gy, (RBE - 2.91-2.79), up to the total focal dose - 5.6- 7.2 Gy The mean value of the total focal dose per outbreak is 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy in the isoeffect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy by isoeffect). At the second stage, photon therapy (electronic 7-10 MeV or gamma therapy 1.25 MeV) is carried out in standard dose fractionation modes: ROD - 3.0 Gy, 5 times a week and ROD - 2.0 Gy, 5 times a week respectively. Gamma therapy is carried out in case of tumor infiltration of the deep layers of the underlying tissues or damage to the bone structures (ribs) in the regimen: single focal dose - 2.0 Gy, 5 times a week, up to the total course dose of neutron-photon therapy of 60 Gy by isoeffect (100 conv unit VDF). Electronic therapy is carried out in the absence of tumor infiltration of the underlying tissues, in the presence of damage to only the skin and subcutaneous tissue in the regimen: single focal dose - 3.0 Gy, 5 times a week, to a total course dose of 60 Gy neutron-photon therapy according to the isoeffect (100 condition unit VDF). The course dose with the combination of fast neutrons with both gamma therapy and electronic therapy is 60 Gy according to the isoeffect, in terms of the VDF factor - 100 conventional units, which does not exceed the tolerance of normal tissues. The course of neutron-photon therapy of local relapses of breast cancer is 20-25 days.

The proposed method of neutron-photon therapy is used to reduce the duration of radiation therapy and reduce the number of side effects - local radiation reactions of the skin and radiation damage to normal tissue in the irradiation area. So, in the proposed method, the total absorbed dose of fast neutrons of 6.3 MeV on the skin of the irradiation fields is 35.4 ± 8.0 Gy in the isoeffect, which is less than when irradiating patients with local recurrences of breast cancer in the prototype (46-50 Iso effect).

In the proposed method, 6.3 MeV fast neutron radiation therapy for patients with local recurrences of breast cancer is carried out on a U-120 cyclotron, the size of the radiation fields varies from 6 × 8 cm to 10 × 10 cm, RIP - 110 cm. One, two, or three radiation fields. The area of tumor recurrence and surrounding normal tissue are included in the irradiation zone at a distance of at least 3-5 cm in different directions from the tumor foci. A beam of fast neutrons is directed perpendicular to the chest wall. Calculation of the focal dose is carried out at 80% isodose, which is located at a depth of 2-3 cm from the surface of the skin, depending on the magnitude of the radiation field. A single focal dose of 6.3 MeV fast neutrons per focal point is 1.6-2.0 Gy (RBE - 2.91-2.79), on the skin - 2.0-2.2 Gy (RBE - 2.79- 2.73), which, according to the isoeffect of 7.4-8.1 Gy of standard photon radiation, taking into account corrections for RBE, heterogeneity of the fat layer and the size of the enlarged fraction. Spend 3-4 sessions, with an interval of 48-72 hours, to the course dose of fast neutrons to the focus of 5.6-7.2 Gy. The mean value of the total focal dose per outbreak is 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy in the isoeffect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy by isoeffect). In the second stage after neutron therapy, gamma therapy or electronic therapy is carried out depending on the prevalence of local recurrence of breast cancer directly to the area of the recurrent tumor. Gamma therapy is prescribed for tumor infiltration of deep layers of underlying tissues or damage to bone structures (ribs) in the regimen: single focal dose - 2.0 Gy, 5 times a week, up to a total course dose of neutron-photon therapy of 60 Gy by isoeffect (100 conventional unit VDF). Electronic therapy of 7-10 MeV is carried out with the spread of tumor recurrence on the skin and subcutaneous tissue in the mode: single focal dose - 3.0 Gy, 5 times a week, up to a total course dose of neutron-photon therapy of 60 Gy according to the isoeffect (100 conv. units of VDF). In terms of indicators of the VDF factor - 100 conventional units, which does not exceed the tolerance of normal tissues. The duration of neutron-photon therapy is 20-25 days, whereas in the prototype - 28-35 days.

New in the proposed method is that with local relapses of breast cancer at the first stage, 3-4 sessions of 6.3 MeV fast neutron radiation therapy are applied, with an interval of 48-72 hours, to the area of tumor recurrence and surrounding normal tissue at a distance of not less than 3-5 cm in different directions from the tumor foci, with a single focal dose to the lesion - 1.6-2.0 Gy, to the skin - 2.0-2.2 Gy, to the total focal dose to the lesion - 6.6 ± 1 , 5 Gy (27.7 ± 5.8 Gy in isoeffect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy in isoeffect), and in the second stage, depending on the prevalence of local r cidivis is carried out gamma or electronic therapy in standard mode directly to the area of the recurrent tumor, while the total course dose from the two stages of neutron-photon therapy is 60 Gy by isoeffect (100 conventional units of VDF), and the duration of the course does not exceed 20-25 days.

The proposed method of radiation therapy with fast neutrons of 6.3 MeV does not cause skin damage of the II-III degree in the radiation fields, and only pronounced erythema of the radiation fields is manifested. Neutron therapy refers to densely ionizing radiation and is more effective against tumor foci that are resistant to standard photon radiation [3]. The use of neutron therapy in the proposed dose helps to reduce the frequency of acute radiation reactions of the skin, resulting in a reduced exposure time to 20-25 days, against 28-35 days in the prototype. The addition of neutron photon therapy (electronic or gamma therapy) can increase the effectiveness of radiation treatment of local relapses, while not causing excessive radiation exposure to the patient's body, since the course dose is 60 Gy by isoeffect (100 conventional units of VDF), which considered a radical dose for treating local relapses in breast cancer. The calculation of the total focal dose of fast neutrons 6.3 MeV and the heading dose of mixed neutron-photon irradiation is carried out using the mathematical model of VDF [4].

Thus, to achieve the maximum effect in the treatment of local recurrences of breast cancer, radiation therapy is carried out with 6.3 MeV fast neutrons and photons. Moreover, in comparison with the prototype, at the first stage, 3-4 sessions of 6.3 MeV fast neutron radiation therapy are carried out in a total focal dose of 6.6 ± 1.5 Gy, which reduces the effect of neutron radiation on the skin of the radiation fields (8.3 ± 1 , 3 Gy), and then additionally at the second stage, photon therapy (gamma therapy or electronic therapy) is prescribed directly to the area of the recurrent tumor according to standard methods. The total course dose of neutron-photon therapy is 60 Gy according to the isoeffect (100 conventional units of VDF).

A method of treating local relapses of breast cancer is carried out in two stages. At the first stage, patients are prescribed 3-4 sessions of 6.3 MeV fast neutron radiation therapy, with an interval between sessions of 48-72 hours, directly to the area of tumor recurrence and surrounding normal tissue at a distance of at least 3-5 cm from the tumor foci, a single focal dose to the outbreak - 1.6-2.0 Gy, to the skin - 2.0-2.2 Gy, to the total focal dose to the outbreak - 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy isoeffect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy in isoeffect). A beam of fast neutrons is directed perpendicular to the chest wall. At the second stage, photon therapy is carried out in standard dose fractionation modes (electronic 7-10 MeV or gamma therapy 1.25 MeV), depending on the indications and nature of the local relapse. Gamma therapy is carried out in case of tumor infiltration of the deep layers of the underlying tissues or damage to the bone structures (ribs) in the regimen: single focal dose - 2.0 Gy, 5 times a week, up to the total course dose of neutron-photon therapy of 60 Gy by isoeffect (100 conv unit VDF). Electronic therapy is carried out in the absence of tumor infiltration of the underlying tissues, in the presence of damage to only the skin and subcutaneous tissue in the regimen: single focal dose - 3.0 Gy, 5 times a week, to a total course dose of 60 Gy neutron-photon therapy according to the isoeffect (100 condition unit VDF). The course dose with the combination of fast neutrons with both gamma therapy and electronic therapy is 60 Gy according to the isoeffect (100 conventional units of VDF). The duration of neutron-photon therapy for local recurrences of breast cancer is 20-25 days.

According to the proposed method, 27 patients with primary and repeated local relapses of breast cancer T2-4N0-2M0 were treated. The follow-up period for patients who received a course of neutron-photon therapy was 12-36 months (median - 27 months).

We present clinical examples of the method:

Example 1: Patient T., 71, medical history No. 119987. Diagnosis: Cancer of the right breast T3N0M0, condition after neo- and adjuvant chemotherapy according to the CMF scheme (standard doses), radical mastitis by Patty, postoperative remote gamma therapy in standard mode for regional lymph drainage zones (1999). Histological diagnosis: infiltrative lobular cancer. In 2002, a tumor recurred in the area of the postoperative scar, represented by multiple tumor nodules 0.3-0.4 cm in diameter. Regarding relapse, neutron-photon therapy was performed in the ROD mode - 1.76 Gy, 4 sessions, 2 times a week, SOD - 7.04 Gy, which corresponds to 30 Gy of standard photon irradiation. Neutron therapy was supplemented by electronic therapy in the regime of ROD - 3.0 Gy, 8 sessions, 24 Gy, which amounted to 30 Gy by isoeffect. The course dose is 60 Gy by isoeffect. The exposure time was 21 days. There was no radiation reaction in the irradiation zone. The relapse-free follow-up period is 16 months.

Example 2. Patient M., 47 years old, case history No. 125818. Diagnosis: Cancer of the left breast T2N1M0, condition after 1 course of neoadjuvant chemotherapy according to the CMF scheme, radical mastectomy according to Peyty, postoperative remote gamma-therapy in standard mode for regional lymphatic drainage zones SOD 40 Gy (1998). Histological diagnosis: infiltrative ductal cancer with metastases to the lymph nodes. In 2001, a relapse of the tumor in the area of the postoperative scar was diagnosed. At the first stage, neutron therapy was prescribed in the following mode: ROD per outbreak - 1.6 Gy, 4 sessions, SOD - 6.4 Gy, which corresponds to 26 Gy by isoeffect. Additionally, electronic radiation therapy was carried out: ROD - 3.0 Gy, 9 sessions, SOD - 27 Gy or 34 Gy by isoeffect. The course dose of mixed irradiation is 60 Gy according to the isoeffect. The exposure duration was 23 days, radiation reactions on the skin were not observed. The relapse-free observation period in the patient is 2 years.

Example 3. Patient Ch., 49 years old, medical history No. 123075. Diagnosis: Cancer of the left breast T4N2M0, condition after courses of neo- and adjuvant chemotherapy according to the schemes CMF, CAF (standard doses), radical mastectomy according to Patty, postoperative remote gamma therapy in a standard mode on the zones of regional lymph drainage SOD 40 Gy (2001). Histological diagnosis: infiltrative lobular cancer, with metastases to the lymph nodes. In 2002, a relapse of the tumor in the area of the postoperative scar was diagnosed. Regarding the relapse, radiation therapy with fast electrons of 7 MeV was performed, in the regime: ROD - 3.0 Gy, 16 sessions, SOD - 60 Gy by isoeffect. In 2003, the progression of the disease: repeated relapse in the area of the postoperative scar (in the area of previous exposure) (figure 1). Given the tumor's resistance to photon radiation therapy, the patient was prescribed neutron-photon therapy in the regimen: ROD - 1.76 Gy, 4 sessions, SOD - 7.04 Gy or 30 Gy by isoeffect, then electronic therapy in the ROD mode - 3.0 Gy, 8 sessions, SOD - 30 Gy by isoeffect. The course dose of neutron-photon therapy was 60 Gy according to the isoeffect. The exposure time was 25 days. A radiation reaction in the form of erythema, which was stopped after 5 days using laser therapy. The relapse-free period is 10 months (figure 2).

Thus, as a result of the proposed method, the duration of radiation therapy is reduced, the number of side effects — local radiation reactions of the skin and radiation injuries of normal tissue in the places of radiation — is reduced, while the effectiveness of neutron-photon therapy does not decrease, since the course dose is 60 Gy isoeffect (100 conventional units of VDF), which is considered a radical dose for the treatment of local relapses of breast cancer.

Information sources

1. Khmelevsky E.V. Radiation therapy of relapse of breast cancer // Oncology issues. - 1999. - T. 45, No. 5. - S.560-564.

2. Slonimskaya E.M., Musabaeva L.I., Shagiakhmetova R.A., Yalova M.F. Neutron therapy in the complex treatment of locally advanced breast cancer. // In the book. Fast neutrons in oncology. - Tomsk: NTL Publishing House, 2000. pp. 143-156 (prototype).

3. Musabaeva L.I. Radiation therapy with fast neutrons with an average energy of 6 MeV of radioresistant malignant neoplasms. Abstract. diss. MD L, 1991 .-- 41 p.

4. Lisin V.A. VDF model for remote therapy of malignant tumors with fast neutrons // Med. Radiology - 1988. - No. 9. - S.9-12.

Claims (1)

A method of treating local relapses of breast cancer, which consists of conducting 6.3 MeV fast neutron radiation therapy 2 times a week, characterized in that the treatment is carried out in two stages: in the first stage, 3-4 neutron therapy sessions are prescribed with an interval of 48-72 hours directly to the area of tumor recurrence and surrounding normal tissues at a distance of at least 3-5 cm from the tumor foci, with a single dose to the lesion - 1.6-2.0 Gy, the relative biological effectiveness of which was 2.91-2.79, skin - 2.0-2.2 Gy, to the total dose per outbreak - 6.6 ± 1.5 Gy, per skin - 8.3 ± 1.3 Gy, at the second stage, gamma or electronic therapy is carried out with a single focal dose of 2.0-3.0 Gy, 5 fractions per week, while the total course dose of neutron-photon radiation to the focus is 60 Iso effect, or 100 conventional units VDF factor with a duration of exposure of 20-25 days.

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