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ONCOLOGY AND RADIOLOGY
INVENTION
Patent of the Russian Federation RU2286818

METHOD OF TREATMENT OF LOCAL RECURRESTS OF BREAST CANCER

The name of the inventor: Lyudmila Musabaeva (RU); Zhogina Zhanna Aleksandrovna (RU); Great Victoria Valerievna (RU); Lisin Valery Andreevich (RU)
The name of the patent holder: State Institution Research Institute of Oncology of the Tomsk Scientific Center of the Siberian Branch of the Russian Academy of Medical Sciences (State Research Institute of Oncology, Siberian Branch of the Russian Academy of Medical Sciences) (RU)
Address for correspondence: 634009, Tomsk, per. Cooperative, 5, State Research Institute of Oncology, Pat. P. G.D. Tsesarskoy
Date of commencement of the patent: 2004.05.25

The invention relates to the field of medicine, in particular to oncology. The method allows to shorten the time of radiotherapy and reduce the number of side effects - local radiation reactions of the skin and radiation damage to normal tissues in places of irradiation. Radiation therapy is carried out with fast neutrons 6.3 MeV 2 times a week, which is carried out in two stages: in the first stage 3-4 sessions of neutron therapy are prescribed with an interval of 48-72 hours directly to the tumor recurrence area and surrounding normal tissues at a distance of at least 3 -5 cm from the tumor lesions, single dose to the focus - 1,6-2,0 Gy, the relative biological efficiency of which was 2,91-2,79, on the skin - 2,0-2,2 Gy, up to the total dose on The focus is 6.6 ± 1.5 Gy, on the skin - 8.3 ± 1.3 Gy, in the second stage gamma or electronic therapy is performed with a single focal dose of 2.0-3.0 Gy, 5 fractions per week, with This total exchange rate of neutron-photon irradiation on the source is 60 Gy by the isoelectric effect, or 100 conventional units. Factor VDF with a duration of irradiation course of 20-25 days.

DESCRIPTION OF THE INVENTION

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

Methods are known for treating local recurrences of breast cancer by photon therapy with a 6-22 MeV fast electron beam or 1.25 MeV remote gamma therapy in the area of ​​recurrence of the same half of the anterior thoracic wall and the region of the regional lymph drainage to a total focal dose (SOD) of 44-50 Gy With the subsequent reduction of the volume of irradiated tissue to the local and the introduction of radiation therapy to SOD 56-80 Gy [1].

Disadvantages of these methods are:

  • A large volume of the tissues of the anterior chest that is 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 recurrences of breast cancer is 71.5 ± 8.4% when the total focal dose in the range of 50-80 Gy is used;
  • The development of radioresistance of local relapses to photon radiation therapy in the event of the emergence of a second tumor.

The closest way to treat local recurrences of breast cancer by a positive effect is the method of radiation therapy with fast neutrons 6.3 MeV with a 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 by the isoelectric effect, for 4-5 weeks. At the same time, the total regression of local relapses reached 100% [2] (prototype).

The disadvantage of this method is:

  • Carrying out radiation therapy with fast neutrons 6.3 MeV takes a long time from 4 to 5 weeks (28-35 days);
  • Neutron therapy in its own form causes pronounced side effects in the form of local radiation reactions of irradiated skin areas (2-3 degrees of severity) and radiation damage to normal tissue in places of irradiation in more than 57% of patients.

It is an object of the present invention to shorten the timing of radiotherapy and to reduce the number of side effects-local radiation reactions of the skin and radiation damage to normal tissue at irradiation sites.

This task is achieved in the proposed method in that the treatment is carried out in two stages: in 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 on the tumor recurrence area and surrounding the normal tissue at a distance Not less than 3-5 cm in different directions from the tumor sites, 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 to the focus is 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy by the isoelectric effect), the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy By the isoelectric effect). At the second stage, photon therapy (electronic 7-10 MeV or gamma-therapy 1.25 MeV) is carried out in standard dose fractionation regimes: RPM - 3.0 Gy, 5 times a week and ROD - 2.0 Gy, 5 times a week respectively. Gamma-therapy is performed with tumor infiltration of deep layers of underlying tissues or lesions of bone structures (ribs) in the regime: a single focal dose of 2.0 Gy, 5 times a week, up to the total exchange rate of neutron-photon therapy of 60 Gy according to the isoelectric effect (100 usl VDF). Electronic therapy is performed in the absence of tumor infiltration of the underlying tissues, in the presence of lesions of only the skin and subcutaneous tissue in the regime: a single focal dose of 3.0 Gy, 5 times a week, up to a total exchange rate of neutrophil therapy of 60 Gy by isoeffect (100 usl VDF). The course dose with a combination of fast neutrons with both gamma therapy and electronic therapy is 60 Gy for the isoelectric effect, in terms of the VDF factor - 100 units, which does not exceed the tolerance of normal tissues. The course of neutron-photon therapy of local recurrences of breast cancer is 20-25 days.

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

In the proposed method, radiation therapy with fast neutrons 6.3 MeV in patients with local recurrences of breast cancer is carried out on a cyclotron U-120, the sizes of irradiation fields vary from 6 × 8 cm to 10 × 10 cm, RIP - 110 cm. One, two, Or three irradiation fields. The irradiation zone includes the area of ​​tumor recurrence and surrounding normal tissue at a distance of at least 3-5 cm in different directions from the tumor sites. A beam of fast neutrons is directed perpendicularly to the chest wall. Calculation of the focal dose is carried out by 80% isodose, which is located at a depth of 2-3 cm from the surface of the skin, depending on the magnitude of the irradiation field. A single focal dose of fast neutrons of 6.3 MeV is 1.6-2.0 Gy at the focus (RBE = 2.91-2.79), on the skin 2.0-2.2 Gy (RBE = 2.79- 2.73), according to the isoelectric effect of 7.4-8.1 Gy of standard photon radiation, taking into account the RBE corrections, the heterogeneity of the fat layer and the size of the enlarged fraction. Conduct 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 to the focus is 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy by the isoelectric effect), the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy By the isoelectric effect). In the second stage, after neutron therapy, gamma therapy or electronic therapy is performed depending on the prevalence of local recurrence of breast cancer directly on the area of ​​the recurrent tumor. Gamma-therapy is prescribed for tumor infiltration of deep layers of underlying tissues or lesions of bone structures (ribs) in the regime: a single focal dose of 2.0 Gy, 5 times a week, up to a total exchange rate of neutrophil therapy of 60 Gy by isoeffect (100 usl VDF). Electronic therapy of 7-10 MeV is carried out with the spread of tumor recurrence on the skin and in the subcutaneous tissue in the regime: a single focal dose of 3.0 Gy, 5 times a week, up to the total exchange rate of neutron-photon therapy of 60 Gy by isoeffect (100 conv. Units VDF). In terms of factors 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 at local recurrences of breast cancer at the first stage 3-4 fast neutron therapy sessions 6.3 MeV, with an interval of 48-72 hours, on the area of ​​tumor recurrence and surrounding normal tissue at a distance of at least 3-5 cm in different directions from the tumor sites, a single focal dose to the focus - 1,6-2,0 Gy, to the skin - 2,0-2,2 Gy, up to the total focal dose to the focus - 6,6 ± 1 , 5 Gy (27.7 ± 5.8 Gy by the isoelectric effect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy by the isoelectric effect), and in the second stage, depending on the prevalence of local relapse Conduct gamma or electronic therapy in the standard mode directly on the area of ​​a recurrent tumor, with the total course dose from the two stages of neutron-photon therapy being 60 Gy for the isoelectric effect (100 units of VDF), and the duration of the course does not exceed 20-25 days .

The proposed method of radiation therapy with fast neutrons 6.3 MeV does not cause skin damage of II-III degree in the fields of irradiation, but is manifested only by pronounced erythema of the irradiation fields. Neutron therapy refers to dense ionizing radiation and is more effective against tumor centers resistant to standard photon radiation [3]. The use of neutron therapy in the proposed dose reduces the frequency of acute radiation reactions of the skin, which reduces the duration of irradiation to 20-25 days, against 28-35 days in the prototype. The addition of neutron therapy to photon (electron or gamma therapy) makes it possible to increase the efficiency of radiotherapy of local relapses without causing excessive radiation stress on the patient's body, since the value of the exchange rate is 60 Gy for the isoelectric effect (100 units of VDF), which Is considered a radical dose for the treatment of local recurrences of breast cancer. Calculation of the total focal dose of fast neutrons 6.3 MeV and the exchange dose of mixed neutron-photon irradiation is carried out using the mathematical model of VDF [4].

Thus, to achieve maximum effect in the treatment of local recurrences of breast cancer, radiation therapy is carried out by fast neutrons 6.3 MeV and photons. In this case, in comparison with the prototype, 3-4 sessions of radiation therapy with fast neutrons of 6.3 MeV in the total focal dose of 6.6 ± 1.5 Gy are carried out at the first stage, which reduces the influence of neutron radiation on the skin of irradiation fields (8.3 ± 1 , 3 Gy), and then additionally in the second stage, photon therapy (gamma therapy or electronic therapy) is administered directly to the region of the recurrent tumor by a standard procedure. The total exchange rate of neutron-photon therapy is 60 Gy for the isoelectric effect (100 units of VDF).

The method of treatment of local recurrences of breast cancer is carried out in two stages. At the first stage, patients are assigned 3-4 sessions of radiation therapy with fast neutrons 6.3 MeV, with an interval between sessions of 48-72 hours, directly on the tumor recurrence area and surrounding normal tissue at a distance of not less than 3-5 cm from the tumor focuses, single focal The dose to the focus was 1.6-2.0 Gy, the skin - 2.0-2.2 Gy, up to the total focal dose to the focus - 6.6 ± 1.5 Gy (27.7 ± 5.8 Gy by Isoeffect), on the skin - 8.3 ± 1.3 Gy (35.4 ± 8.0 Gy by the isoelectric effect). A beam of fast neutrons is directed perpendicularly to the chest wall. At the second stage, photon therapy is performed in standard dose fractionation regimes (electronic 7-10 MeV or gamma therapy 1.25 MeV), depending on the indications and the nature of the local relapse. Gamma-therapy is performed with tumor infiltration of deep layers of underlying tissues or lesions of bone structures (ribs) in the regime: a single focal dose of 2.0 Gy, 5 times a week, up to the total exchange rate of neutron-photon therapy of 60 Gy by isoeffect (100 usl VDF). Electronic therapy is performed in the absence of tumor infiltration of the underlying tissues, in the presence of lesions of only the skin and subcutaneous tissue in the regime: a single focal dose of 3.0 Gy, 5 times a week, up to a total exchange rate of neutrophil therapy of 60 Gy by isoeffect (100 usl VDF). The rate dose for combination of fast neutrons with both gamma therapy and electronic therapy is 60 Gy for the isoelectric effect (100 VED units). The duration of neutron-photon therapy of local recurrences of breast cancer is 20-25 days.

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

Here are some clinical examples of the method:

Example 1
Patient T., 71, No. 119987. Diagnosis: Right breast cancer T3N0M0, condition after neo-and adjuvant chemotherapy according to the CMF (standard dose) regimen, radical mastectomy by Peyti, postoperative distance gamma-therapy in standard mode at Zones of regional lymph drainage (1999). Histological diagnosis: infiltrative lobular cancer. In 2002, a tumor recurrence in the postoperative scar area, represented by multiple tumor nodes 0.3-0.4 cm in diameter. With regard to recurrence, neutron-photon therapy was performed in the RPM 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 mode of RPM - 3.0 Gy, 8 sessions, 24 Gy, which is 30 Gy by virtue of the isoelectric effect. The course dose is 60 Gy by the isoelectric effect. The duration of irradiation was 21 days. Radiation reaction in the irradiation zone was absent. Relapse-free observation period - 16 months.

Example 2
Patient M., 47 years old, No. of case history 125818. Diagnosis: Left breast cancer T2N1M0, condition after 1 course of neoadjuvant chemotherapy according to CMF scheme, radical mastectomy by Peyti, postoperative distance gamma-therapy in standard mode to regional lymph drainage zones SOD 40 Gy (1998); Histological diagnosis: infiltrative protocol cancer with metastases to the lymph nodes. In 2001, a tumor recurrence was diagnosed in the postoperative scar area. At the first stage, neutron therapy was administered in the following regimens: RPM on the lesion - 1.6 Gy, 4 sessions, SOD - 6.4 Gy, which corresponds to 26 Gy by the isoelectric effect. In addition, electronic radiation therapy was performed: ROD - 3.0 Gy, 9 sessions, SOD - 27 Gy or 34 Gy by isoelectric effect. The course dose of mixed irradiation is 60 Gy by the isoelectric effect. The duration of irradiation was 23 days, no radiation reactions were observed on the skin. Relapse-free observation period in the patient is 2 years.

Example 3
Patient Ch., 49, No. 123075. Diagnosis: Left breast cancer T4N2M0, state after courses of neo-and adjuvant chemotherapy according to CMF, CAF (standard doses), radical mastectomy by Peyti, postoperative distance gamma-therapy in 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 tumor recurrence was diagnosed in the postoperative scar area. Concerning relapse, radiotherapy was performed with fast electrons of 7 MeV, in the regime: RPM - 3.0 Gy, 16 sessions, SOD - 60 Gy by isoelectric effect. In 2003, the disease progressed: repeated relapse in the area of ​​the postoperative scar (in the zone of previous irradiation) (Fig. 1). Taking into account the radioresistance of the tumor to the photon radiation therapy, the patient was assigned neutron-photon therapy in the following regimen: ROD - 1.76 Gy, 4 sessions, SOD - 7.04 Gy or 30 Gy by the isoelectric effect, then electron therapy in the mode of the RPM - 3,0 Gy, 8 sessions, SOD - 30 Gy by the isoelectric effect. The course dose of neutron-photon therapy was 60 Gy for the isoelectric effect. The duration of irradiation was 25 days. The radiation reaction in the form of erythema, which was stopped after 5 days by laser therapy. The recurrence period is 10 months (Fig. 2).

METHOD OF TREATMENT OF LOCAL RECOMMENDATIONS OF BREAST CANCER. Patent of the Russian Federation RU2286818 METHOD OF TREATMENT OF LOCAL RECOMMENDATIONS OF BREAST CANCER. Patent of the Russian Federation RU2286818

Thus, as a result of the proposed method, the terms of radiotherapy are reduced, the number of side effects - local radiation reactions of the skin and radiation damage to normal tissue at the sites of irradiation is reduced, while the efficiency of neutron-photon therapy is not reduced, since the exchange rate is 60 Gy by Isoeffect (100 units of VDF), which is considered a radical dose for the treatment of local recurrences of breast cancer.

INFORMATION SOURCES

  1. Khmelevsky E.V. Radiation therapy of recurrences of breast cancer / / Oncology. - 1999. - Т.45, №5. - P.560-564.

  2. Slonimskaya EM, Musabaeva LI, Shagiakhmetova RA, Yalova MF Neutron therapy in the complex treatment of locally advanced breast cancer. // In the book. Fast neutrons in oncology. - Tomsk: Publishing house of NTL, 2000. p.143-156 (prototype).

  3. Musabaeva L.I. Radiation therapy with fast neutrons of average energy of 6 MeV of radioresistant malignant neoplasms. Author's abstract. Diss. Ph.D. L, 1991. - 41 p.

  4. Lisin V.A. Model VDF for remote therapy of malignant tumors by fast neutrons // Med. Radiology - 1988. - №9. - C.9-12.

CLAIM

The method of treatment of local recurrences of breast cancer, consisting of fast neutron therapy 6.3 MeV 2 times a week, characterized in that the treatment is carried out in two stages: at the first stage 3-4 sessions of neutron therapy are prescribed with an interval of 48-72 h , Directly to the tumor recurrence area and surrounding normal tissues at a distance of at least 3-5 cm from the tumor sites, a single dose to the focus of 1.6-2.0 Gy, the relative biological efficiency of which was 2.91-2.79, per Skin - 2,0-2,2 Gy, up to the total dose to the focus - 6,6 ± 1,5 Gy, on the skin - 8,3 ± 1,3 Gy, in the second stage gamma or electronic therapy is performed with a single focal dose 2.0-3.0 Gy, 5 fractions per week, the total exchange rate of neutron-photon irradiation on the source is 60 Gy by the isoelectric effect, or 100 conventional units. Factor VDF with a duration of irradiation course of 20-25 days.

print version
Date of publication 25.11.2006гг