RU2748135C2 - Method for combined treatment of locally advanced forms of cervical cancer iib-iiib (t2b-t3bn0(1)m0) stages - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to the field of pharmaceuticals, namely to a method for combined treatment of locally advanced forms of cervical cancer IIB-IIIB (T2b-T3bN0(1)M0) stages. The method includes the first stage of treatment, during which 2 courses of neoadjuvant polychemotherapy are carried out with an interval of 21 days: intravenous administration of paclitaxel and cisplatin in certain doses in the form of a 3-hour infusion with previous premedication, as well as 30 minutes before the administration of paclitaxel, intramuscular administration of dexamethasone or intra-arterial administration of cisplatin at a certain dose, alternately in the right and left uterine arteries and the next day, intravenous administration of paclitaxel is performed in the form of a 3-hour infusion with previous premedication, as well as 30 minutes before the administration of paclitaxel intramuscular administration of dexamethasone, 21 days after the last course of chemotherapy, combined chemoradiation therapy is carried out: distance - 3D conformal radiation therapy or intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy - VMAT of the small pelvis and areas of regional metastasis. The total boost dose is 46-50 Gy. The fractionation mode is 2 Gy daily 5 times per week. Moreover, during remote irradiation as a radiomodification - cisplatin is administered at a certain dose, at 4-5 weeks of irradiation on days free from remote irradiation, brachytherapy is performed in 4 fractions of 7 Gy to the total boost dose equivalent of 30 Gy, total doses from the course combined radiation therapy are: in t. A 80-90 Gy, in t. B 60 Gy, and the volume of irradiation directly includes the primary tumor, the parametric region, sacro-uterine ligaments, the optimal distance from the edge of the primary tumor is not less than 3 cm, taking into account the level of tumor lesions of the vagina, the group of pelvic lymph nodes, as well as all other regional lymph nodes.

EFFECT: invention improves efficiency of treatment of patients with locally advanced cervical cancer by increasing the overall and disease-free survival rates, as well as improving the quality of life.

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Description

The invention relates to medicine, namely to oncology, and can be used to treat locally advanced cervical cancer (CC).

Radiation therapy is the main treatment for locally advanced cervical cancer. However, today there is no optimal tactics for the treatment of cervical cancer, which would ensure the achievement of a high therapeutic effect and long-term survival of patients, therefore the most important task of modern gynecological oncology remains the development and implementation of rational approaches in the treatment of this pathology.

Known methods of treating locally advanced cervical cancer, including radiation therapy with radiomodification drugs, radiation treatment using various schemes of cytostatics, combined radiation therapy (Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Cancer II Trial. Samantha Cabral S da Costa, Renata Colombo Bonadio, Flavia Carolina G Gabrielli, Andrea S Aranha, Maria Luiza N Dias Genta, Vanessa C Miranda, Daniela de Freitas, Elias Abdo Filho, Patrícia AO Ferreira, Karime K Machado, Mariana Scaranti , Heloísa de A Carvalho, Maria Del Pilar Estevez-Diz // J Clin Oncol, 2019, Nov 20; 37 (33): 3124-3131; Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study.Gabriella Ferrandina, Eleonora Palluzzi, Valerio Gallotta, Maria Antonietta Gambacorta, Rosa Autor ino, Luigi Carlo Turco, Gabriella Macchia, Francesco Cosentino, Benedetta Gui, Maria Vittoria Mattoli, Graziana Ronzino, Vincenzo Valentini, Giovanni Scambia // Eur J Surg Oncol, 2018, Jul; 44 (7): 1062-1068).

The disadvantage of the method of combined radiation therapy using radiomodification is the insufficient supply of drugs to the irradiated area due to fibrotic changes and vascular hardening that develop as a result of radiation therapy.

The therapeutic possibilities of radiation therapy for locally advanced cervical cancer are limited by the size of the tumor. It has been established that as the volume of the primary tumor focus increases by the time of the start of treatment, the indicator of the effectiveness of radiation treatment is steadily decreasing. Conducting combined radiation therapy with the use of increased doses of radiation in patients with locally advanced cervical cancer leads to a decrease in the frequency of local recurrence, but radiation damage to tissues and organs of the small pelvis limits a further increase in the dose. radiation therapy does not effectively control metastases to the paraaortic retroperitoneal lymph nodes, which are observed in 30% of patients with a locally advanced process, and does not affect the growth of distant metastases.

A known method for the treatment of cervical cancer, which provides for the intravenous administration of anticancer chemotherapy drugs before radiation therapy. Scheme of intravenous administration of 5-fluorouracil 750 mg / m² 1-4 days (4 days in total at a dose of 4-5 g) and Cisplatin at a dose of 80 mg / m² (Guide to the chemotherapy of tumor diseases / Ed. By N.I. Perevodchikova. - 2nd ed. Additional - M .: Practical medicine, 2005, - 704 p .; Survival and toxicity in neoadjuvant chemotherapy plus surgery versus definitive chemoradiotherapy for cervical cancer: A systematic review and meta-analysis. C Marchetti, A Fagotti, V Tombolini, G Scambia, F De Felice // Cancer Treat Rev. 2020 Feb; 83: 101945).

The disadvantages of this method are low efficiency and severity of toxic side effects. The known method does not allow achieving the same clinical response as the method presented by us.

The known method of neoadjuvant chemotherapy for cervical cancer, which includes 2 courses with the introduction of drugs cisplatin at a dose of 75 mg / m ² intraarterially, selectively catheterizing the internal iliac arteries (RU 2405544 C1).

However, the known method does not allow achieving the same clinical response as the method we propose.

The technical result is to increase the effectiveness of treatment of patients with locally advanced cervical cancer by increasing the overall and disease-free survival rates, as well as improving the quality of life.

A feature of the proposed method is that at the first stage, 2 courses of neoadjuvant polychemotherapy (PCT) are carried out with an interval of 21 days by various routes of administration: intravenous administration of paclitaxel at a dose of 175 mg / m²and cisplatin at a dose of 75 mg / m²in the form of a 3-hour infusion with previous premedication 12 and 6 hours, as well as 30 minutes before the administration of paclitaxel, intramuscular administration of 20 mg of dexamethasone and intra-arterial administration of cisplatin at a dose of 75 mg / m²for 400 ml of saline, alternately in the right and left uterine arteries, 200.0 ml of the finished solution at a rate of 3-4 ml / min and the next day intravenous administration of paclitaxel at a dose of 175 mg / m is performed²in the form of a 3-hour infusion with previous premedication 12 and 6 hours, as well as 30 minutes before the administration of paclitaxel, intramuscular administration of 20 mg of dexamethasone, then 21 days after the last course of chemotherapy, combined chemoradiotherapy is carried out: distance - 3D conformal radiation therapy and beam intensity modulated radiation therapy (IMRT), volume modulated arc therapy (VMAT) of the small pelvis and areas of regional metastasis SOD 46-50 Gy fractionation mode 2 Gy daily 5 times a week, and during remote irradiation as a radio modification - enter cisplatin at a dose of 40 mg / m², moreover, brachytherapy is carried out at 4-5 weeks of irradiation on days free from remote irradiation, in 4 fractions of 7 Gy up to SOD equivalent to 30 Gy, the total doses from the course of combined radiation therapy are: in point A 80-90 Gy, in t 60 Gy, and the planned volume of irradiation directly includes the primary tumor, the parametric area, the sacro-uterine ligaments, the optimal indentation from the edge of the primary tumor of at least 3 cm, taking into account the level of tumor lesions in the vagina, a group of pelvic lymph nodes, and all other regional lymph nodes. In the absence of a detected metastatic lesion in the iliac lymph nodes, the volume of irradiation includes the group of external, internal iliac and obturator lymph nodes. In cases of diagnosing metastatic lesions in the iliac and / or para-aortic lymph nodes, an extended border of the irradiation area is used, and the upper border of the field reaches the level of L1-L2 vertebrae, and if a group of paraortal lymph nodes is affected, then the upper border of the field reaches the Th12 level. In case of damage to regional lymph nodes, the total dose is increased to 10-15 Gy in the form of a local boost. The clinical volume of the irradiation target (CTV) is divided into three zones CTV1, CTV2, CTV3:

- CTV1 includes the tumor, the cervix and the entire uterus;

- CTV2 captures the parametria and the entire vaginal part of the tumor +2 cm below its most distal part, and the border of the parameters includes: anterior - the bladder wall, posterior - perisacral fascia, medial - the edge of the tumor and lateral - the pelvic wall;

- CTV3 includes common, external and internal iliac and presacral lymph nodes with a 7 mm entrapment around vessels or any visible lymph nodes, cysts, while CTV3 does not extend to adjacent bowel loops, bones or muscles, and should not extend above the bifurcation of the aorta, starting not below the intervertebral space L4-5, and the presacral lymph nodes are delineated to the upper border of the body S3, and the external iliac l / nodes are delineated to the level of the exit of the external iliac vessels from the small pelvis, and if the distal third of the vagina is involved in the tumor process, the inguinal l / nodes are delineated as a continuation of CTV3 from the external lymph nodes down to the level of 2 cm caudal to the sapheno-femoral junction, and in the case of involvement of the para-aortic lymph nodes, the boundaries are: upper - the top of Th12, lower - aortic bifurcation, laterally - along the level of the transverse processes of the vertebrae, each volume of CTV increase due to allowances for the planned target volume (PTV):

PTV 1 - CTV1 + 15 mm,

PTV 2 - CTV2 + 10 mm,

PTV 3 - CTV3 + 7 mm.

The method is carried out as follows.

Neoadjuvant chemotherapy is carried out, consisting of 2 courses with an interval of 21 days by various routes of administration:

1. Intravenous administration of paclitaxel at a dose of 175 mg / m ² and cisplatin at a dose of 75 mg / m ² in the form of a 3-hour infusion with premedication 12 and 6 hours before, and also 30 minutes before the administration of paclitaxel, intramuscular administration of 20 mg of dexamethasone.

2. Intra-arterial administration of cisplatin at a dose of 75mg / m ² to 400 ml of physiological saline, alternately in the right and left uterine arteries by 200.0 mL of the prepared solution at a rate of 3-4 ml / min and the next day perform intravenous administration of paclitaxel at a dose of 175mg / m ² in the form of a 3-hour infusion with previous premedication for 12 and 6 hours, as well as 30 minutes before the introduction of paclitaxel, intramuscular injection of 20 mg of dexamethasone.

21 days after the last course of chemotherapy, combined chemoradiation therapy is performed: distance - 3D conformal radiation therapy of the small pelvis and areas of regional metastasis SOD 46-50 Gy (IMRT). Fractionation mode 2Gy daily 5 times a week. As a radiomodification, cisplatin is administered at a dose of 40 mg / m2 during remote irradiation. Beginning of brachytherapy at 4-5 weeks of irradiation on days free from remote irradiation.

Fractionation mode: 4 fractions of 7 Gr. to SOD eq. 30 gr. Total doses from the course of combined radiation therapy: including A 80-90 Gy, including B 60 Gy.

The planned volume of irradiation includes the primary tumor itself, the parametric area, the sacro-uterine ligaments, the optimal indentation from the edge of the primary tumor, at least 3 cm, taking into account the level of tumor lesions in the vagina, a group of pelvic lymph nodes, as well as all other regional lymph nodes.

In the absence of a detected metastatic lesion in the iliac lymph nodes after the initial comprehensive examination, the group of external, internal iliac and obturator lymph nodes was included in the irradiation volume.

In cases of diagnosing metastatic lesions of the iliac and / or para-aortic lymph nodes, the extension of the borders of the irradiation area is applied, the upper border of the field reaches the level of L1-L2 vertebrae, or, taking into account the level of damage to the group of paraortal lymph nodes, respectively, the upper border of the field reaches the Th12 level.

An increase in total doses to the region of regional lymph nodes in case of their damage is additionally permissible within the range of 10-15 Gy in the form of a local boost.

The use of IMRT and other conformal irradiation methodologies is auxiliary in order to reduce the dose load on the intestines and other organs of risk in the plans of irradiation, as well as in cases of the need for irradiation of the paraaortic region.

Determine the irradiated CTV volumes (clinical target volume) that divided into three zones: CTV1, CTV2, CTV3.

CTV1 includes a tumor - the cervix and the entire uterus.

CTV2 captures the parametria and the entire vaginal part of the tumor +2 cm below its most distal part. The boundary of the parameters includes: anterior - the bladder wall, posterior - perisacral fascia, medial - the edge of the tumor, lateral - the pelvic wall.

CTV3 includes common, external and internal iliac and presacral lymph nodes with a 7 mm engagement around the vessels or any visible lymph nodes, cysts.

Moreover, CTV3 should not extend to adjacent bowel loops, bones, or muscles. Upper limit CTV3 should not extend above the aortic bifurcation, starting at least below the L4-5 intervertebral space. Presacral lymph nodes are outlined to the upper border of the body S3. The external iliac l / nodes are contoured to the level of the exit of the external iliac vessels from the small pelvis.

In case of involvement of the distal third of the vagina in the tumor process, the inguinal l / nodes should be contoured as a continuation of CTV3 from the external lymph nodes down to the level of 2 cm caudal to the sapheno-femoral junction.

In the case of involvement of the para-aortic lymph nodes, the boundaries are as follows: the upper one is the apex of Th12, the lower one is the bifurcation of the aorta, laterally - almost at the level of the transverse processes of the vertebrae.

Each CTV volume is increased due to allowances for: PTV (planned target volume) PTV 1 (CTV1 + 15 mm), PTV 2 (CTV2 + 10 mm), PTV 3 (CTV3 + 7 mm).

Clinical testing of the method was carried out in 35 patients with locally advanced cervical cancer IIB-IIIB (T2b-T3bN0 (1) M0) stages. The average age of the patients was 37.7 ± 1.2 years (at the age of 35-45 years - 40% of patients). Squamous cell carcinoma of the cervix uteri was diagnosed in 70% of patients and adenocarcinoma in 30% of patients. The size of the tumor more than 4 cm in diameter was observed in 85% of patients, in 15% of patients the size of the primary tumor was from 2 to 4 cm.

After the first course of neoadjuvant polychemotherapy, partial regression was observed in 40% of patients, stabilization of the process - in 60% of cases. Complete regression of the tumor focus, as well as the progression of the process, was not observed. After the second course of chemotherapy, partial tumor regression was observed - in 70%. Stabilization of the tumor process was noted in 30% of cases. The tolerability of the polychemotherapy courses was satisfactory.

The toxicity of tolerance of polychemotherapy was assessed in 2 groups of patients. In the group of patients with intra-arterial injection of the drug, grade I leukopenia was noted in 30% of patients, in the systemic PCT group, grade I leukopenia was noted in 20% and grade II in 30% of patients. Polyneuropathy in the group with intra-arterial injection was noted for I degree in 5% of patients and in the group of systemic PCT in 10% of patients. All complications were corrected and the patients tolerated satisfactorily. After completion of chemoradiation therapy, the toxicity of treatment tolerance was also evaluated. Radiation enterocolitis I degree (RTOG) in two groups of patients was 60% and II degree (RTOG) - 30%, respectively. Radiation rectitis was noted in two groups I degree (RTOG) and amounted to 6%, cystitis I and II degrees (RTOG) was noted in both groups and amounted to 12% in each. Grade I nausea and vomiting (RTOG) was 20% in the intra-arterial injection group and 30% in the systemic PCT group, respectively. The therapy was carried out with eubiotics, antiemetics with a positive effect, radiation reactions were stopped and the patients tolerated satisfactorily. All patients underwent treatment of the vaginal mucosa with antiseptics and ointments with anti-inflammatory and regenerative effects. There were no interruptions in treatment.

The follow-up period of the patients ranged from 3 to 18 months, the median follow-up was 12 months. No late radiation injuries were noted during the indicated observation periods. After the combined chemoradiation therapy, the progression of the disease was detected in 1 patient in the systemic PCT group in the form of the appearance of distant metastases to the supraclavicular lymph nodes, and in 2 patients in the group with intra-arterial chemoinfusion in the form of metastases to the ovaries and distant metastases to the supraclavicular lymph nodes, complete regression of the primary tumors - in 91.4% of cases, partial regression - in 8.6%.

The use of neoadjuvant polychemotherapy followed by chemoradiation therapy in patients with locally advanced cervical cancer leads to a decrease in the incidence of distant metastases, local relapses, and an increase in 5-year survival. A decrease in tumor volume, a decrease in pain syndrome, cessation or reduction of bleeding from the genitals increase the effectiveness of combined chemoradiation therapy in the second stage. Consistent use of chemotherapy and radiation therapy reduces the toxicity of the treatment.

The proposed 3D conformal and IMRT, VMAT beam planning method allowed:

- to increase efficiency due to optimal irradiation parameters;

- reduce the risk of radiation damage and reduce toxicity, thereby ensuring a high quality of life;

- local dose escalation;

- safely expand the volume of radiation to the para-aortic region and the entire small pelvis with maximum protection of critical organs and healthy tissues.

Clinical examples.

Example # 1

Patient Zh., 44 years old, was in the Department of Radiation Therapy of the Moscow Oncological Research Institute. P.A. Herzen - a branch of the Federal State Budgetary Institution "NMIRC" of the Ministry of Health of Russia in 2019 with a clinical diagnosis of IIIB cervical cancer (ycT2bN1M0).

From the anamnesis: The patient from September 2018 notes spotting from the genital tract. I went to the gynecologist at the place of residence. A cytological study was performed, according to which the pathology of the cervix was diagnosed. In December 2018, a biopsy of the cervix with WFD was performed. According to the histological study: fragments of glandular fibrous endometrial polyps with a vascular "pedicle" without atypia and fragments of the cervix of the cervix with a picture of moderately differentiated squamous cell carcinoma infiltrative throughout the entire thickness with tumor invasion of vascular cracks, partly represented by layers of squamous cell carcinoma without an underlying base.

Ultrasound of the abdominal cavity, small pelvis, regional zones (01/25/19 - before treatment): para-aortic, paracaval, in the iliac vessels - no focal formations were detected. The uterus is slightly enlarged. The cervix of the uterus is tumor-altered - a tuberous tumor measuring 60x39x42mm, extending to the lower part of the uterus to a height of 21-23mm, extending into the left parametrium up to 12mm. Conclusion: echographic picture of the cervix Cr with spread to the body of the uterus, parametrium on the left.

MRI of the pelvic organs (01/30/19 - before treatment): a circular tumor of the cervix without clear contours is determined, located mainly on the left: - at the level of the upper sections it involves the left semicircle of the stromal ring, extending to the internal pharynx, infiltrates the lower part of the uterine body, involves the fornices of the vagina, the largest axial dimensions are 52x51mm, the vertical length is 58mm. In the right obturator area, the changed l / u up to 18x11mm, in the left obturator area up to 5mm along the short axis. Single l / y in the mesorectal tissue up to 5 mm. Conclusion: MR is a picture of a tumor of the cervix, with spread to the body of the uterus, with the involvement of the internal pharynx and external pharynx, anterior and lateral vaginal vaults, anterior vaginal wall, with access to the paracolpium. Metastatic obturator lymph nodes. SCC (01/18/19): 9.9ng / ml.

In the first stage of combined treatment conducted 2 courses of systemic chemotherapy with an interval of 21 days according to the scheme: paclitaxel 175mg / ^m2 + Cisplatin 75 mg / m ^2. At the control examination after 2 courses of PCT: ultrasound of the abdominal cavity, small pelvis, regional zones (04/15/19): para-aortic, paracaval, along the iliac vessels - without focal zones. The cervix measuring 45x25x36.5mm, with tumor changes 39x17x30mm, is not reliably located on the body of the uterus. MRI of the small pelvis (04/06/19): in comparison with MRI before treatment - positive dynamics. The cervix measuring 21x40x46mm with clear uneven contours due to exophytic formation measuring 42x32x29mm (previously 58x52x51mm) with clear uneven contours, extending over the entire thickness of the stromal ring, into the vagina with the involvement of the fornices, with signs of the process entering the parametrium to a depth of at least 4.5mm on the left, 4 mm on the right. The formation extends to the level of the internal pharynx (previously it spread to the body of the uterus). Conclusion: MRI - a picture of the formation of the cervix with signs of the process entering the right and left parameters - positive dynamics.

SCC (05.14.19g) - 4.1 ng / ml.

The patient was discussed at a consultation on 05/14/19 with the participation of radiologists, surgeons, chemotherapists, according to the control examination, there is a positive trend in the form of a decrease in the tumor process in the cervix, but the resectability of the process is doubtful. Thus, in the second stage of combined treatment, combined radiation therapy according to a radical program is indicated.

In the second stage of the combined treatment, a course of combined chemoradiation therapy was performed in the pelvic area. Remote 3 D conformal beam ROD-2Gy, up to SOD = 50Gy. Radimodification with the drug cisplatin 40 mg / m ² (OD 160 mg). Intracavitary gamma therapy was carried out on the “MultiSource” apparatus by introducing the metracolpostat system into the uterine cavity and lateral vaginal vaults, ROD-7 Gr x 4 sessions. Irradiation rhythm 2 times a week. SOD eq 30Gy.

The patient was under strict dynamic observation for 15 months. No data were found for relapse of the disease.

Example No. 2

Patient K., 39 years old, was in the Department of Radiation Therapy of the Moscow Oncological Research Institute. P.A. Herzen - a branch of the FSBI "NMIRC" of the Ministry of Health of Russia in 2019 with a clinical diagnosis of IIB cervical cancer (yT2bN0M0).

From the anamnesis: was observed for a long time about erosion and ectropion of the cervix. 12/25/18 in GBUZ "Primorskaya KKB No. 1" - knife biopsy of the cervix, curettage of the cervical canal; embolization of the uterine arteries. Histological report No. 6081-6085: CIN H-W, HSIL, structures of microinvasive cancer with detectable invasion up to 3.5 mm. According to MPT OMT, ultrasound OMT revealed locally advanced cervical cancer - tumor size 4x3x6 cm, there was parametric infiltration on the left with a length of more than 2 cm, to a depth of 18 mm; there was also spread of the tumor to the upper third of the vagina and to the isthmus of the uterus. For further treatment and examination, she turned to the Moscow Oncological Institute. The histological conclusion (horse, in MNIOI 19 / 1-247): Squamous cell keratinizing moderately differentiated cervical cancer.

02/11/2019 SCC tumor marker = 6.3 ng / ml.

02/06/2019 Uzi omt: In the groin areas, enlarged l / nodes are not detected. The rectal wall is not changed. The body of the uterus: determined in the usual position, the dimensions are not increased, length 52.5 mm, thickness 35.2 mm, width 57 mm. The structure of the myometrium is weakly diffusely heterogeneous. M-echo: thickness is slightly uneven, thickness is 7 mm, structure is echo-positive, moderately heterogeneous, in i / Z-s / Z - a zone with dimensions of 16x6.4x14 mm is of greater echogenicity, without registered vascularization, with clear, fairly even contours, vascularization is not detected ... Uterine cavity: not expanded. Cervix: length 39 mm, thickness 44 mm, width 60 mm (with transabdominal access - 39x36x60 mm); the form is usual; solid structure, hypoechoic, with pronounced pathological vascularization, mss max. = 21.3 cm / s ir min. 0.33. Elastographically, elasticity is non-uniform. Almost completely the cervix is replaced by a tumor, measuring 40.5x29x59 mm, the shape is irregular, the contours are uneven. On the right - without convincing signs of parametrium infiltration. On the left - signs of parametric invasion with a length of more than 2 cm, to a depth of 18 mm., There are signs of spreading to the walls of the vagina in in / 3. Endocervix: not differentiated. Cervical canal: not dilated. The left ovary: determined by dimensions - length 31.2 mm, thickness mm, width 32 mm, follicles in it are not determined, the zone is weakly hypoechoic with peripheral vascularization - a corpus luteum? Up to 13.2 mm. Right ovary: defined, length 26 mm, thickness 17 mm, width 20 mm, a single follicle with dimensions of 13x14 mm, without hypervascularization. Fluid in the posterior space: not detected. Pathological formations in the pelvic area: not identified. The veins of the plexus of the pelvis are without pronounced features, the width of the lumen is up to 4-5 mm.

In the first stage of the course 2 held regional chemotherapy, with an interval of 21 days of cisplatin 75 mg intraarterially + paclitaxel 175 mg / ^m2 Day 2.

At the control examination after 2 courses of RPHT ultrasound OMT (04/01/19): in the inguinal and iliac regions, the enlarged l / nodes are not determined. The rectal wall is not changed. The body of the uterus: determined in the usual position, the dimensions are not increased, length 40.5 mm, thickness 31 mm, width 50 mm. The structure of the myometrium is weakly diffusely heterogeneous. M-echo: thickness 4.5 mm, echo-positive structure, homogeneous, with clear, fairly even contours, vascularization was not detected. Uterine cavity: not expanded. Cervix: length 34 mm, thickness 24 mm, width 38 mm (with transabdominal access - 3x36x60 mm); the form is usual; the structure is solid, hypoechoic, with pronounced pathological vascularization. Elastographically, elasticity is non-uniform. The posterior wall of the cervix is almost completely replaced by a tumor measuring 32x23x48 mm, the shape is irregular, the contours are uneven. On the right - without convincing signs of parametrium infiltration. Left - signs of parametric invasion up to 17 cm long, to a depth of about 10 mm. There were no signs of the spread of the VA wall of the vagina in the / 3. At the level of the isthmus - a single cyst dm 7 mm. Endocervix: not differentiated. Cervical canal: not dilated. Left ovary: determined by dimensions - length 28 mm, thickness mm, width 24 mm, with a single anechoic inclusion dm 9 mm. Right ovary: defined, length 12 mm, thickness 9 mm, width 14 mm, afollicular, without hypervascularization; clear contours, requires observation. Fluid in the posterior space: not detected. Pathological formations in the pelvic area: not identified. The veins of the plexus of the pelvis are without pronounced features, the width of the lumen is up to 4-5 mm. Conclusion: cervical cancer st2bnxm0. Signs of spread to the isthmus of the uterus, to the left parametrium. There are signs of positive dynamics in the form of regression of changes in / 3 of the vagina, a decrease in the size of the tumor, parametric infiltration on the left. 03/27/19 Tumor marker SCC = 0 μg / L.

10.04.2019 Laparoscopic ovarian transposition, bilateral tubectomy.

Discussed at the council on 04/05/19, Given the presence of parametric infiltration, the vaginal variant of the tumor process, radical surgical treatment is doubtful, it is planned to carry out chemoradiation treatment according to a radical program.

In the second stage of the combined treatment, a course of combined chemoradiation therapy was performed in the pelvic area. Remote 3 D conformal beam ROD-2Gy, up to SOD = 50Gy. Radimodification with the drug cisplatin 40 mg / m ² (OD 200 mg). Intracavitary gamma therapy was carried out on the “MultiSource” apparatus by introducing the metracolpostat system into the uterine cavity and lateral vaginal vaults, ROD-7 Gr x 4 sessions. Irradiation rhythm 2 times a week. SOD eq 30Gy.

The patient was under strict dynamic observation for 15 months. No data were found for relapse of the disease.

The proposed method in clinical practice will allow achieving a faster regression of the primary focus, increasing the effectiveness of radiation therapy and improving the quality of life of patients.

Claims (2)

1. A method of combined treatment of locally advanced forms of cervical cancer IIB-IIIB (T2b-T3bN0 (1) M0) stages, characterized by the fact that at the first stage 2 courses of neoadjuvant polychemotherapy (PCT) are carried out with an interval of 21 days: intravenous administration of paclitaxel 175 mg / m ² and cisplatin at a dose of 75 mg / m ² as a three-hour infusion preceding premedication for 12 and 6 hours and 30 minutes before administration of paclitaxel intramuscular administration of 20 mg of dexamethasone or intraarterial administration of cisplatin at a dose of 75 mg / m ² per 400 ml of saline, alternately in the right and left uterine arteries, 200.0 ml of the finished solution at a rate of 3-4 ml / min and the next day intravenous administration of paclitaxel at a dose of 175 mg / m ² in the form of a three-hour infusion is performed with previous premedication 12 and 6 hours, as well as 30 minutes before the administration of paclitaxel, intramuscular administration of 20 mg of dexamethasone, 21 days after the last course of chemotherapy, combined chemotherapy is administered study therapy: external - 3D conformal radiation therapy or radiation therapy with beam intensity modulation (IMRT), or therapy with volume modulation - VMAT of the small pelvis and areas of regional metastasis SOD 46-50 Gy fractionation mode 2 Gy daily 5 times a week, and during remote irradiation as a radiomodification - cisplatin is administered at a dose of 40 mg / m ² , at the 4-5th week of irradiation on days free from remote irradiation, brachytherapy is performed in 4 fractions of 7 Gy to SOD equivalent to 30 Gy, total doses from the course of combined radiation therapy are: in t. A 80-90 Gy, in t. B 60 Gy, and the planned volume of irradiation includes directly the primary tumor, the parametric region, sacro-uterine ligaments, the optimal distance from the edge of the primary tumor is not less than 3 cm, taking into account the level of tumor lesions of the vagina, the group of pelvic lymph nodes, as well as all other regional lymph nodes. 2. The method according to claim 1, characterized in that in the absence of a detected metastatic lesion in the iliac lymph nodes, the irradiation volume includes a group of external, internal iliac and obturator lymph nodes.