RU2444386C1 - Method for local recurrence prevention in patients suffering locally advanced breast cancer t2-4n1-3m0-1 with unfavourable prognostics - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to oncology, and can be used for the purpose of radiation therapy of locally advanced forms of breast cancer T_2-4N_1-3M_0-1 with unfavourable prognostics. A postoperative cicatrix is exposed to fast neutron 6.3 MeV within 3 sessions from two or three fields of radiation, in single radiation dose - 1.4-1.76 Gy to total isoeffective basic dose - 25-32 Gy.

EFFECT: method provides reducing a number of recurrences and complications.

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Description

The invention relates to medicine, in particular to oncology, and can be used in radiation therapy of locally advanced forms of breast cancer T _2-4 N _1-3 M _0-1 with unfavorable prognostic signs.

A known method for the combined treatment of locally advanced forms of breast cancer by applying a preoperative fast neutron course of 6.3 MeV: a single focal dose of ROD - 2.4 Gy, three sessions, with an interval after 48-72 hours, the total focal dose - 7.2 Gy, which the isoeffect is 38–40 Gy of standard photon therapy [1].

The disadvantages of this method are:

- The inability to conduct a scar on patients in the postoperative period due to the absence of a mammary gland;

- The use of a large single and total dose of fast neutrons - 2.4 Gy - 7.2 Gy, which is 38-40 Gy according to the isoeffect, on the postoperative scar, which can lead to the occurrence of radiation injuries of normal tissues and organs adjacent to the chest wall.

A known method of treating patients with common local recurrences of breast cancer, which consists in conducting radiation therapy with fast neutrons of 6.3 MeV 2 times a week, a single focal dose of 1.6-2.0 Gy (RBE - 2.91-2.79), on the skin, 2.0-2.2 Gy, up to the total dose of fast neutrons per focus - 6.6 ± 1.5 Gy and on the skin - 8.3 ± 1.3 Gy at the first stage, and then continue treatment with electronic or gamma -therapy with standard courses up to a radical dose of 60 Gy according to the isoeffect (100 conventional units of the VDF factor indicator) with an irradiation course duration of 20-25 days.

The disadvantages of this method are:

- A long course of mixed neutron-photon therapy according to the radical SOD program - 60 isoGy due to the presence of a locally advanced tumor;

- Severe radiation reactions of the skin and subcutaneous tissue after neutron-photon therapy (analogue) [2].

Closest to the proposed one is a method of radiation therapy with an electron beam of 7-10 MeV per postoperative scar with a single focal dose of ROD - 3.0 Gy, 5 times a week, SOD - 40-44 Gy by isoeffect in patients with locally advanced forms of breast cancer T _2-4 N _1-3 M ₀ with the presence of adverse clinical and morphological factors of prognosis after radical or conditionally radical mastectomy [3].

The disadvantages of this method are:

- Duration of exposure for 2- - 2.5- weeks;

- The relapse rate in the area of the postoperative scar is 6.4% (6 cases out of 94 patients) in patients in the first two years after radiation therapy in the control group.

A new technical task is to increase the effectiveness of treatment by reducing the number of relapses while reducing the duration of the treatment course.

To solve the problem in a method for the prevention of local recurrence in patients with locally advanced breast cancer T _2-4 N _1-3 M ₀ with unfavorable prognostic signs by means of radiation therapy with an electron beam on a postoperative scar, characterized in that they are affected by 6.3 MeV fast neutrons for 3 sessions, from two to three radiation fields, with a single focal dose - 1.4-1.76 Gy to the total focal dose - 25-32 Gy according to the isoeffect.

The method is as follows. Patients with a high risk of local recurrence: edematous-infiltrative form of breast cancer, multicentric tumor growth, angiolymphatic invasion into surrounding tissues and other unfavorable signs (Table 1, which describes the high risk factors for local recurrence in patients with breast cancer T _2-44 N _{1 -3} M _0-1 (n-28)) carry out 6.3 MeV fast neutron radiation therapy in the area of the postoperative scar, for example, at the U-120 cyclotron of Tomsk Polytechnic University. Due to the high degree of risk of local recurrence of the disease in the postoperative scar, breast cancer patients are treated in the regimen: twice a week, from two or three radiation fields 8 × 6 cm ² or 10 × 10 cm ² after removal of the mammary gland. The dimensions of the radiation fields correspond to the length of the postoperative scar (from 10 cm to 20 cm) with the inclusion of surrounding tissues at a distance of 5 cm in different directions from the scar.

A single dose of 6.3 MeV fast neutrons per skin varies between 1.75-2.2 Gy, and 1.4-1.76 Gy per focus. Three sessions are carried out, with an interval of 48-72 hours, the total focal dose (SOD) is 16.7-25 isoGy, on the skin - 25.6-32Gy according to the isoeffect.

The mode of the proposed method is based on the analysis of the results of clinical observations of 28 patients.

Patients with primary forms of breast cancer T _2-4 N _1-3 M _0-1 with adverse prognostic signs and a high risk of local recurrence after radical or conditionally radical mastectomy were prescribed neutron therapy, only 3 sessions, per postoperative scar, without additional use in this area gamma or electron radiation therapy. Used mainly 2-3 radiation fields: 8 × 6 cm ² , 10 × 10 cm ² , a single focal dose - 1.4-1.76 Gy, while a single dose on the skin of the irradiated field is 1.75-2, 2 gr. The total focal dose for three sessions is 16.7-25 isoGy, on the skin of the irradiation fields - 25.6-32 isoGy. After completion of the neutron therapy course (3 sessions), all 28 patients with a locally advanced process underwent a standard DHT for regional lymphatic drainage zones in the LAR - 2.0 Gy to SOD - 40 - 44 Gy for the postoperative scar. In all breast cancer patients, systemic chemotherapy or antiestrogen therapy was used (if indicated). As can be seen from table 1, in addition to the high risk of local recurrence in 5 patients, distant metastases to the bones and lungs were additionally detected before the development of the developed treatment method. The median of observation of 28 patients in the group with neutron therapy by the proposed method was two years. According to the results of relapse-free survival, this group of patients was compared with the prototype group [3].

The results of treatment in the group with postoperative scar irradiation with fast neutrons of 6.3 MeV.

Clinical testing of the application of the proposed method for the prevention of local recurrence by neutron therapy for postoperative scar in 28 patients with breast cancer T _2-4 N _1-3 M _0-1 with unfavorable prognosis factors showed its satisfactory tolerance. Radiation reactions of the skin were moderate, did not require additional treatment. Only in 2 (7%) cases out of 28 patients, moist epidermitis was observed in the radiation fields, which required the appointment of magnetic laser therapy. Radiation reaction of the lungs - pneumonitis and local pneumofibrosis were diagnosed after 4-6 months. 3 (11%) of 28 patients with breast cancer. They were corrected with antibacterial, hormonal drugs with a positive effect.

The two-year relapse-free survival of breast cancer patients T _2-4 N _1-3 M _0-1 , who underwent neutron therapy on a scored scar according to the proposed method, was 100%, whereas in the prototype, where patients received electronic therapy for a postoperative scar in SOD 40-44, Gy, the number of local relapses over two years was 6.4% (6 cases out of 94 patients).

Clinical example 1. Patient C., 59 years old, No. of case history 01101.

Diagnosis: Cancer of the left mammary gland T ₄ N ₂ M ₁ , secondary-edematous infiltrative form. MTS in the left ilium (Oct. 2006). The condition after 3 courses of neoadjuvant chemotherapy according to the CAF regimen and 3 courses of NHT according to the taxotere regimen (treatment tactics changed due to progression along the main focus). Condition after radical mastectomy from 05/08/2007.

Pathomorphological study No. 18990-91 / 08 of 10.23.06 - infiltrating ductal cancer 2 tbsp. malignancy. Receptor status is positive: ER (76% / 196) and RP (85% / 212). Her2neu expression is negative (1+).

05/31/07, 4 courses of chemotherapy were conducted with taxotere.

Taking into account unfavorable prognostic factors, from 06/26/07 to 07/03/07, neutron therapy was carried out on the area of the postoperative scar with 2 radiation fields: 8 × 6 cm ² , ROD - 1.76 Gy (80% isodose, at a depth of 2-2.5 cm), 3 sessions, 2 times a week, on the skin - ROD - 2.2 Gy. The total course dose to the focus was 24.5 isoGy, to the skin of the irradiation fields - 32 isoGy. Tolerance of neutron therapy was quite satisfactory. After the third session, moderate hyperemia of the skin in the irradiation zone was noted, which was stopped by the appointment of methyluracil ointment. Postoperative remote gamma-therapy in standard mode in an SOD of 42 Gy was additionally performed in the regions of regional lymph drainage. The relapse-free observation period in the patient was 2.5 years. No radiation damage from the skin of the irradiation fields and postoperative scar, lung tissue was noted.

Example 2. Patient M., 42, No. of medical history 07339.

Diagnosis: Cancer of the right breast T ₄ N ₃ M ₀ , inflammatory edematous-infiltrative form. Condition after 6 courses of neoadjuvant chemotherapy according to the RAS scheme, radical mastectomy from 08.13.2009

Pathomorphological study: multicentric invasive carcinoma of the 3rd degree of malignancy with metastases of 11 l / y. The receptor status is negative: RE and RP are negative. Expression of Her2neu - (2+).

On October 15, 2009, 1 course of adjuvant chemotherapy was carried out according to the scheme: cisplatin 140 mg and Navelbin 40 mg. Taking into account the existing unfavorable prognosis factors in the patient, from 20.10.09 to 27.10.09, 3 neutron therapy sessions were conducted in the area of the postoperative scar: ROD - 1.4 Gy (80% isodose), ROD on the skin - 1.75 Gy, SOD - 4 , 2 Gr. The course SOD was 17 isoGy, on the skin - 25 isoGy. Two irradiation fields were used: 8 × 6 cm ² . The patient tolerance of neutron therapy was quite satisfactory. No radiation reaction of normal tissues (skin, lung tissue) was noted.

Additionally, in the standard metastasis zone from 10/21/09 to 11/30/09, DHT was performed in the standard mode up to SOD - 44 Gy, then systemic chemotherapy according to the above scheme: cisplatin, Navelbin.

During follow-up: after 8 months after neutron therapy data for the development of local recurrence and distant metastasis of the disease in the patient were not received. No radiation damage to normal tissues (skin, lungs) is observed.

Thus, the proposed method allows to reduce the number of relapses and complications while reducing the course of treatment.

Table 1 Unfavorable prognosis factors Abs. hours (%) Locoregional prevalence of the primary tumor: p T1-2N2-3, 23 (82%) p T3N1-3, p T4NO-3 metastatic breast cancer: r T1-4M1-3M1 5 (18%) edematous forms of breast cancer 13 (47%) multicentric growth, invasion of the lymphatic vessels, germination tumors in the dermis 21 (75%) Receptor negative tumors 13 (47%) Saved menstrual function 19 (68%)

Information sources

1. RF patent No. 2186591 of 08/10/2002. The method of neutron-photon therapy of locally advanced breast cancer // L.I. Musabaeva, V.A. Lisin, E.M. Slonimskaya.

2. RF patent No. 2286818 from 10.11.06. A method of treating local relapses of breast cancer / L.I. Musabaev, J.A. Zhogin, V.V. Velikaya, V.A. Lisin.

3. Kharchenko V.P., Khmelevsky E.V., Chkhikvadze V.D., Bozhenko V.K., Panshin G.A., Kolesnikov R.V. Features of development and risk factors for postmastectomy local regional relapse of breast cancer // Oncology Issues. 2009.- T.55. - No. 4, p. (Prototype).

Claims (1)

A method for the prevention of local recurrence in patients with locally advanced breast cancer T _2-4 N _1-3 M _0-1 with unfavorable prognostic signs by radiation therapy with an electron beam on a postoperative scar, characterized in that they are affected by 6.3 MeV fast neutrons for 3 sessions from two to three radiation fields, with a single focal dose of 1.4-1.76 Gy to a total focal dose of 25-32 Gy according to the isoeffect.