RU2478374C1 - Method of intracavitary therapy in treatment of patients with cancer metastases into vagina - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine. Course of chemotherapy with intravenous drop introduction of 100 mg/m² of cisplatin, doxorubicin - 30 mg/m² and vincristine - 4 mg/m² is carried out. After distant gamma-therapy with bringing onto initial focus and regional lymph nodes of total dose 20 Gy, 11-12 sessions of intracavitary Co therapy by two fractions in 2.5 Gy with 5-hour interval, with rhythm 2 times per week alternating with distant gamma-therapy on regional lymph nodes and weekly intravenous introduction of 250 mg of 5-fluorofuracyl at all stages of irradiation.

EFFECT: application of claimed method makes it possible to increase single and total focus doses in intracavitary irradiation, improve results of combined radiotherapy, reduce reactions to normal tissues of adjacent organs and improve life quality of patients with cancer of said localisation in the process of treatment.

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Description

The invention relates to medicine, namely to oncology, and can be used to treat patients with cancer metastases in the middle and lower third of the vagina.

A known method of treating vaginal cancer (Oncogynecology:

A guide for doctors. / Ed. Z.S.Gilyazutdinova and K.M. Mikhailov. - M .: MEDpress, 2000. -. S.201), involving the implementation of combined radiation therapy. Remote gamma-therapy is used to influence the areas of regional metastasis and partially on the primary tumor focus at the level of the total focal dose of 20 Gy. When the tumor is localized in the lower third of the vagina during remote irradiation, part of the dose is delivered from the perineal field and the inguinal lymph nodes are necessarily included in the volume of exposure. Contact radiation therapy is carried out with a single dose of 3 Gy 2-3 times a week, in total - 18-21 Gy and interstitial irradiation at a dose of 40-45 Gy. Interstitial irradiation with Cs-137 preparations is recommended to be carried out on the Microselectron apparatus. The total dose in the tumor with such combined intracavitary therapy is 60-70 Gy. In a common process, radiation treatment is supplemented with drug therapy. The five-year survival rate after radiation therapy for stage III vaginal cancer is 25–40%, and for stage IV –– 0–22%.

The disadvantage of this method is that in order to supply a sufficient carcinogenic dose to the tumor site in the vagina, additional use of interstitial introduction of radioactive needles into the tumor under intravenous anesthesia is necessary. Unfortunately, not all radiological clinics are equipped with the necessary equipment and such capabilities. In addition, the combination of intracavitary and interstitial irradiation is fraught with the development of a significant number of radiation complications.

There is a method of treating vaginal cancer (Bohman YV. "Guide to Oncogynecology. - St. Petersburg:" Publishing House Foliant "2002. S.193-194), located in its middle and lower thirds. For endovaginal irradiation, according to the characteristics of the tumor, special masks are prepared from wax, where Co ⁶⁰ preparations are implanted. The amount of absorbed dose from intracavitary irradiation is individualized depending on the dynamics of tumor regression, clinical and cytological data. In between sessions of intracavitary gamma-therapy, uniform remote irradiation of the pelvis (40-50 Gy) is performed. 5-year survival after treatment is at stage III - 48%.

The disadvantages of this method include the need to make special applicators from wax, the difficulty of fixing them in the vagina, the use of radioactive sources of low dose rate, the duration of the irradiation session, and a large radiation load on the staff.

There is a method of treating malignant tumors (Therapeutic Radiology: A Guide for Doctors. / Ed. By Academician of RAMS, Professor A.F. Tsyba, Corresponding Member of RAMS, Professor Yu.S. Mardynsky. - M.: MK LLC, 2010 , S.18-19), selected by us as a prototype. The method includes the use of daily crushing doses into several fractions, the interval between which should be within 3-6 hours. Due to the increase in the daily dose of radiation, the hyperfractionated radiation therapy technique provides a more complete suppression of tumor growth with a gentle effect on normal tissues, i.e. allows you to extend the radiotherapy interval. The prospect of using hyperfractionated radiation with crushing of the daily dose has been confirmed in many localizations of cancer. However, this approach was not used when performing intracavitary irradiation.

The aim of the present invention is to improve the results of treatment of patients with cancer metastases in the vagina.

The goal was achieved in that patients with cancer metastases in the vagina begin treatment with the introduction of cisplatin - 100 mg / m ² on the 1st day, doxorubicin - 30 mg / m ² and vincristine - 4 mg / m ² intravenously. After 7-10 days, remote gamma therapy is started with open fields, including the primary lesion, in a single focal dose of 2 Gy to a total focal dose of 20 Gy. Then, 2 times a week, intracavitary radiation therapy is carried out depending on the localization of the process with a colpostat with sources along the axis of the vagina. When intracavitary therapy is connected, external radiation (in alternating sessions) is carried out only on the regional lymphatic collector. At the same time, 250 mg of 5-fluorouracil is administered intravenously 1 time per week from the beginning and at all stages of radiation treatment.

Intracavitary Co ⁶⁰ therapy is carried out on an AGAT-B3 apparatus using fractionation of ROD 5 Gy. However, the planned dose is let down for 2 fractions of 2.5 Gy with an interval of 5 hours. In total, in the regime of accelerated fractionation with crushing of the daily dose, 11-12 sessions of intracavitary irradiation are carried out, up to a dose of 65 ± 13.1 isoGy (VDF 102 ± 2.5 units). The total focal dose to the primary lesion, taking into account the dose from external exposure, is at the level of 85 ± 2.5 isoGy (VDF 135 ± 4.2 units), for lymph nodes - 40 Gy (VDF 65 units).

The invention is new, as it is unknown from the level of medicine in the field of oncology in the treatment of cancer metastases in the vagina using alternating distance radiation and radiomodified intracavitary therapy.

The novelty of the invention lies in the fact that in the treatment of patients with cancer metastases in the vagina, the regime of hyperfractionation of the daily dose of radiation is used.

The invention has an inventive step, since it is unknown to an oncologist in this field and does not explicitly follow from the level of clinical oncology.

More significant damage to tumor cells during irradiation with a daily dose fragmentation of 2.5 Gy and an interval between two fractions of it at intervals of 5 hours is explained not only by the summation of the biological effects of irradiation and radiosensitizers. The process of reoxygenation, which begins immediately after the first fractions of radiation, is important. In turn, reoxygenation leads to the inclusion of tumor cells in the cell cycle and partial synchronization, the result of which is an increase in their sensitivity to repeated irradiation.

In accessible sources of information in Russia, the CIS countries and abroad, no indications of a similar method for improving the results of treatment of patients with advanced vaginal cancer have been found.

The invention is industrially applicable, as it can be repeatedly reproduced and used in healthcare, in medical institutions of a specialized profile.

The method is as follows:

On day 1, intravenous drip of cisplatin is carried out - 100 mg / m ² (with a regime of hyperhydration and forced diuresis), doxorubicin - 30 mg / m ² and vincristine - 4 mg / m ² intravenously.

After 10-14 days, remote irradiation is performed. When the lesion is localized in the middle third, it is carried out on the pelvic organs with 2 opposite rhomboid fields 15-16 × 15-16 cm in size (lower border of the field at the level of the borders of the entrance to the vagina), RIC 75 cm. ROD 2 Gy daily 5 fractions per week to SOD 20 Gy (VDF 33 units). When the tumor is located in the lower third of the vagina, the perineal radiation field is used.

Once a week, at first and at all stages of radiation treatment, 250 mg of 5-fluorouracil is administered intravenously.

After a total dose of 20 Gy, intracavitary Co ⁶⁰ therapy is connected to AGAT-B3 using a colpostat included in the standard apparatus. Topometric preparation, specifying the real and planned position of the sources (simulators introduced into the colpospost), is carried out using the ERGA-MP electro-radiological prefix. The dose distribution, taking into account the depth of the lesion, the calculation of the time of the exposure session is carried out according to the Atlas of dose distributions attached to the set of equipment (EP. 197.002 D), series III, No. 35-39.

The irradiation zone along the length of the vagina is individualized in accordance with the size of the lesion. In situations where the process is limited, radiation is localized to the area of clinically pronounced lesions. At the same time, the shortening of the radiating system is ensured by using standard lead filters so that the active ends of the sources (or 1 preparation) are 1.5-2 cm longer than the lesion length on each side. With multicentric distribution, the radiation sources are located along the entire length of the vagina. With a local tumor focus, special protective shields from tungsten are introduced into the colpostat, which allows limiting the irradiation area and protecting neighboring healthy organs and tissues.

Used fractionation mode ROD 5 Gy. The daily dose, in our proposed method, is administered in two separate fractions of 2.5 Gy with an interval of 5 hours. Given the coefficient taking into account the break between the sessions, the daily equivalent focal dose is 5.6 ± 10.2 isoGy.

Intracavitary therapy sessions alternate with external exposure only to regional metastasis zones.

In total, in the regime of accelerated fractionation with crushing of the daily dose, 11-12 sessions of intracavitary irradiation are performed. The total dose from intracavitary irradiation is 65 ± 3.1 isoGy (VDF 102 ± 2.5 units). The total focal dose to the primary lesion, taking into account the dose from external exposure, is at the level of 85 ± 2.5 isoGy (VDF 135 ± 4.2 units), for lymph nodes - 40 Gy (VDF 65 units). For the course of treatment, the total dose of cytostatics is 100 mg / m ² , doxorubicin - 30 mg / m ² , vincristine - 4 mg / m ² and 1750 ± 250 mg of 5-fluorouracil.

Adjuvant to all patients with an interval of 3-4 weeks, 3 courses of polychemotherapy of cisplatin 100 mg / m ² , doxorubicin 30 mg / m ² and 400 mg / m ² cyclophosphane are recommended.

As an example of effectiveness, we cite the medical history. Patient S., born in 1944 (source. Bol. No. 841 / e), is under the supervision of RNII since 17.01.08.

Complaints when referring to spotting from the vagina, difficulty urinating, pain in the perineum. From the anamnesis - in 2001 at the place of residence a combination radiation therapy was performed for cervical cancer T2N0M0.

GA No. 17522/01 - squamous cell carcinoma without keratinization with invasive growth of 2.5 mm.

From the presented certificate of treatment, it was established that remote gamma therapy was performed from 4 opposite diluted fields on AGAT-S and intracavitary Co ⁶⁰ therapy on AGAT-B. The total total doses were at point A 72 Gy, at point B 40 Gy, on the bladder 42 Gy, on the rectum 37 Gy.

A survey was conducted at the RNII.

Local status 01/17/08 - in the lower third of the vagina on the right wall there is a dense, tuberous, whitish formation 3.5 × 2.5 × 2 cm in size, partially overlapping the lumen of the vagina. Swelling, hyperemia, membranous masses, pain during examination. Infiltration of the underlying tissues extends to the front wall of the vagina and partially to the perineal skin in the form of a tight flattening of 1 cm. Inguinal lymph nodes on the right in the form of a chain 0.5-0.7 cm in size, are not palpated on the left.

The vagina has a high adhesive process, the tissues of the vaginal mucosa are atrophic. The cervix and uterine body are determined by examination through the intestine of normal size. Moderately expressed rectovaginal fiber infiltration. Paravaginal infiltrate does not reach the pelvic wall. In parametric fiber, cicatricial severity of GA No. 565/08 of 01/17/08 (primary lesion) is squamous cell carcinoma without keratinization, foci of necrosis.

CA No 2231 dated 01/17/08 (puncture of the lymph node) - red blood cells, chron cells. inflammation, separately lying groups of atypical cells.

Cystoscopy from 01/17/08 - the cystoscope was inserted with great difficulty. The mucosa of the bladder is moderately hyperemic, in some places, hemorrhages. The mouths of the ureters are slit-like, located symmetrically. The phenomena of chronic cystitis.

Ultrasound MT and OBP 01/18/08 - the structure of the myometrium of the cervix and uterine body is not changed. Vascularization is within normal limits. Cysts of endocervix 3-11 mm in the lower segment of the cervix. Adhesive process, no data for relapse. Paraaortic, iliac lymph nodes are not visualized. In the right inguinal region, hypoechoic lymph nodes up to 1.0 cm, on the left not enlarged. Diffuse changes in the liver parenchyma, chron. cholecystitis, chron. pancreatitis, small microlites of the left kidney.

FLO OGK dated 01/18/08 No. 42 - lungs and heart - age-related changes. 01/18/08 OAK HB - 114 g / l, Er. - 3.4 × 10 ¹² / l, ESR - 35 mm / hour; L - 13.2 × 10 ⁹ / l, pal. - 25%, seg. - 52%, eos. - 1%, mon. - 2%, lim. - twenty%.

01/18/08 OAM - protein - traces, uv. 1018, lake. - 20-22-24x ', erythro. - 1214x 'betrayed., And unchanged., Epithelium. 1-2x '.

Wedge. dz - metastasis in the vagina of cervical cancer T2N1M0, st III, gr. 2.

The RNII consultant recognized the process as unresectable, chemoradiation treatment was recommended.

01/24/08 a course of intravenous chemotherapy was administered, drip 150 mg of cisplatin (hyperhydration and forced diuresis regimen), 50 mg of doxorubicin, 10 mg of vincristine.

02/01/08. HB - 108 g / l, Er. - 3.6 × 10 ¹² / l, ESR - 22 mm / hour; L - 7.1 × 10 ⁹ / l, pal. - 15%, seg. - 68%, eos. - 1%, mon. - 2%, lim. - fourteen%.

From 02/04/08 to 02/15/08, remote gamma therapy was performed on the AGAT-R through the perineal field 5 × 6 cm, at an angle of 35 °, RIC 75 cm, dose regulation to a depth of 4 cm, a single dose of 2 Gy to a total dose of 20 Gy (VDF 33 units).

Local status 02/18/08 - in the lower third of the vagina on the right wall there is a dense, tuberous whitish formation 3.0 × 1.5 × 1 cm in size. Tissue infiltration is significantly less, the perineal skin is mobile.

02/18/08 HB - 110 g / l, Er. - 3.1 × 10 ¹² / l, ESR - 16 mm / hour; L - 3.9 × 10 ⁹ / l, pal. - 8%, seg. - 72%, eos. - 0%, mon - 3%, lim. - 17%.

02/18/08 OAM - protein - traces, uv. 1015, lake. - 10-14x ', erythro. - 4-5x 'betrayal., And unchanged., Epithelium. 4x

02/19/08; 02/22/08; 02/26/08; 02/29/08; 03/04/08; 03/07/08; 03/11/08; 03/14/08; 03/18/08; 03/21/08 and 03/25/08 conducted 11 sessions of intracavitary With ⁶⁰ therapy on AGAT-B3. Used 3 radioactive sources introduced into the colpostat. A single dose of 2.5 Gy was administered at 8 and 13 hours. The total dose was 62 isoGy (VDF 105 units).

Local status 02/29/08 - in the lower third of the vagina on the right wall there is a dense, whitish formation measuring 1.0 × 1.0 × 0.7 cm.

From 02/18/08 to 03/12/08, on days free from sessions of intracavitary Co ⁶⁰ therapy, remote gamma therapy was performed on the inguinal-femoral groups of lymph nodes on both sides of the apparatus AGAT-R with fields of 8 × 12 cm, RIC 75 cm, a single dose 3 Gy to a total of 40 isoGy 02/04/08; 02/11/08; 02/18/08; 02/25/08; 03.03.08; 03/10/08 and 03/17/08 intravenously administered 250 mg of 5-fluorouracil. The total dose is 1750 mg.

03.03.08 HB - 110 g / l. Er. - 3.2 × 10 ¹² / l, ESR - 24 mm / hour; L - 3.6 × 10 ⁹ / l, pal. - 12%, seg. - 62%, eos. - 4%, mon - 7%, lim. - fifteen%.

03/24/08 HB - 100 g / l, Er. - 3.0 × 10 ¹² / l, ESR - 18 mm / hour; L - 3.1 × 10 ⁹ / l, pal. - 6%, seg. - 65%, eos. - 5%, mon. - 11%, lim. - 13%.

03/24/08 OAM - protein - no, uv. 1015, lake. - 1-2-4x ', erythro. - 0-2x 'change., Epithelium. 1-2x.

In the course of treatment, the patient underwent traditional anti-inflammatory, detoxification, hemostimulating and symptomatic therapy. The vagina was treated daily using solutions of furatsillin or decoctions of herbs - chamomile, yarrow, St. John's wort, oak bark, the introduction of oil swabs with sea buckthorn oil, karatolin and daily administration of suppositories with methyluracil (or proctosan) daily into the rectum and vaginally.

There was no disturbance in the rhythm of radiation treatment.

Thus, the total focal dose to the primary site of metastasis in the vagina was 82 Gy (VDF 136 units), to the regional zones of the lymph nodes 40 isoGy (VDF 66 units). The total dose of cytostatics is 150 mg of cisplatin, 50 mg of doxorubicin, 10 mg of vincristine and 1750 mg of 5 - fluorouracil.

Local status 03/11/08 - in the lower third of the vagina on the right wall there is a planar tissue seal up to 1 cm in size. The mucous membrane above it is mobile. There is no infiltration of the underlying tissues. The skin of the perineum is soft, mobile. Vaginal clearance is free. Inguinal lymph nodes are not palpable. In parametric fiber, cicatricial stiffness.

Wedge. the diagnosis is metastasis in the vagina of cervical cancer T2N1M0, st III, gr. 2. Condition after chemoradiation treatment. When appearing after 1 month. There are no complaints. Urination is free.

Local status 04/29/08 - tissue atrophy in the lower third of the vagina on the right wall. Mucous pale, thinned. There is no infiltration of the underlying tissues. The skin of the perineum is soft, mobile. Vaginal clearance is free. Inguinal lymph nodes are not palpable. In parametric fiber, cicatricial stiffness.

Cystoscopy from 04.29.08 - the mucous membrane of the bladder is moderately hyperemic. The mouths of the ureters are slit-like, located symmetrically. The phenomena of chronic cystitis.

Ultrasound OBP and MT 04/29/08 - the structure of the myometrium of the cervix and uterine body is not changed. Vascularization is within normal limits. Cysts of endocervix 3-11 mm in the lower segment of the cervix. Adhesive process in the pelvis. Diffuse changes in the liver parenchyma, chron. cholecystitis, chron. pancreatitis, small microlites of the left kidney. Inguinal and retroperitoneal lymph nodes are not visualized. The clinical diagnosis of metastasis in the vagina of cervical cancer T2N1M0, st III, gr. 3. Condition after chemoradiotherapy.

The patient categorically refused to conduct the recommended preventive courses of polychemotherapy.

The patient is observed until December 2011 (3 years 9 months) without signs of relapse of the disease and metastases.

The technical and economic effect of the use of the “Method of intracavitary therapy in the treatment of patients with cancer metastases in the vagina” consists in the possibility of increasing the single and total focal doses during intracavitary irradiation, which improves the results of combined radiation treatment, reduces the response to normal tissues of adjacent organs, improves quality life of patients with cancer of the specified localization during treatment.

Claims (1)

The method of intracavitary therapy in the treatment of patients with cancer metastases in the vagina, including chemotherapy, distance gamotherapy, intracavitary Co ⁶⁰ therapy, characterized in that the first step is a chemotherapy course with an intravenous drip of 100 mg / m ² cisplatin, doxorubicin 30 mg / m ² and vincristine - 4 mg / m ² , then after remote gamotherapy with summing up to the primary lesion and regional lymph nodes with a total dose of 20 Gy, 11-12 sessions of intracavitary are performed. With ⁶⁰ treatments, two fractions of 2.5 Gy with an interval of 5 hours, s rhythm 2 times a week, alternating with remote gamotherapy for regional lymph nodes and with weekly intravenous administration of 250 mg of 5-fluorouracil at all stages of irradiation.