Method for predicting occurrence of early stage cervical carcinoma relapses and/or metastases

FIELD: medicine.

SUBSTANCE: method involves determining absolute value of ratio between lymphocyte number and absolute value of monocyte number in peripheral blood at the end of combine radiation therapy. The ratio is divided by 4.05. The result value being greater than 1, no disease relapse occurrence is predicted during the first observation year. The value being less than 1, tumor growth progress is stated and carcinoma relapse is predicted at the first year after treatment.

EFFECT: enhanced accuracy in detecting pathological process progress before observing clinical manifestations.

1 tbl

 

The invention relates to medicine, namely to gynecology, and can be used for diagnosis before clinical manifestation of recurrence of cervical cancer after combined radiation therapy.

There is a method of determining the human health analysis of peripheral blood in the dynamics of treatment with the assessment of the level of hemoglobin, number of erythrocytes, color index, erythrocyte sedimentation rate; the number of leukocytes, the percentage and absolute content in the blood count segmented neutrophils, lymphocytes and monocytes (Vorob'ev A.I. KN. Guide to Hematology. M, Medicine, 1985).

However, the peripheral blood may change even in the presence of a mild inflammatory process and, given the wide range of standards, their dynamics may not be an indicator of the hidden currents of disease recurrence or the occurrence of metastasis in cancer patients. Radiation therapy or cytotoxic treatment in all patients causes various degrees of dose-dependent inhibition of all peripheral blood. This individual and even changed the indicator at any stage of treatment is not specific for cancer of the differences.

Known clinical method for the diagnosis of recurrent cancer of the cervix, which is the traditional examination in mirrors, bimanual and rectovaginal examination (Bohman AV KN. Manual of gynecology, St. Petersburg, 2002. S-304). In doubtful situations where difficult differential diagnosis between neoplastic infiltration and postradiation stenosis, the use of Cytology, General and biochemical blood tests, excretory urography, radioisotope studies of the kidney, ultrasound examination of the pelvis and lumbar region, computed tomography. Possibly the definition in the dynamics of tumor markers CEA and AFP, although they are not specific to cervical cancer.

Simple enumeration methods for the diagnosis of recurrent cancer of the cervix indicates the complexity of the differential diagnosis of this pathology. However, as the author points out, local and parametrial relapse after radiation treatment of cervical cancer occur due to the fact that some of the cancer cells remained viable. And only after some time when the growth of cancer cells form a tumor site, accessible to palpation, the Clinician can make a diagnosis of “relapse”. Today is set to individual clinical signs and their combinations in the individual prognosis in cervical cancer. However, not all features of clinical course of cancer shake the uterus may be provided and used for the early diagnosis of recurrence. The explanation is that clinicians do not have enough objective evidence that could clarify the prospect of further individual currents of the tumor process. Palliative nature of therapeutic benefits are granted, as a rule, only when the clinical manifestation of the development of recurrent cervical cancer. However if you look at the usual clinical symptoms associated with significant relapse (serous-purulent discharge from the vagina, pain due to compression neuritis obturatorious nerve or sciatic plexus, white, and then blue swelling of the lower limbs), the prospects for their treatment is minimal.

The aim of the invention is the ability to identify the development of the pathological process to clinical manifestations.

This goal is achieved by the fact that at the end of the specific radiation treatment in patients produce analysis of peripheral blood taken from a finger, and determine the ratio of the absolute number of lymphocytes to the absolute number of monocytes, then the obtained value is divided by the index of laboratory standards of 4.05, which is the ratio of these components for healthy persons If the value of the result is equal to or higher than unity state clinical cure and no chance receivabletrade in the first year of observation, while values below one ascertain the presence of continued tumor growth and recurrence of cancer in the near future.

In the process of developing the claimed “a predictor of early recurrence and/or metastasis of cervical cancer were retrospectively analyzed prognostically significant indicators of 105 patients with cervical cancer Tsmgo stage at the end of the standard and methodologically identical combined radiation therapy. All patients were divided into two groups. The first 55 women who have lived 5 years after treatment without signs of recurrence of the disease. The second 50 women who had verified the recurrence of cervical cancer detected during the period from 6 to 12 months.

All patients determined the value of lympho-monocytic index representing the ratio of the absolute number of lymphocytes to the absolute number of monocytes and divided by 4,05.

4,05 is the ratio of the absolute number of lymphocytes to the absolute number of monocytes established in the survey almost 35 healthy women of similar age of the examined patients.

Table 1 presents these lympho-monocytic index both retrospective group of patients before and after combined radiation treatment.

From the table it is seen that maintenance is jovannie patients with cervical cancer TNxMo stage initial values of the analyzed parameters lymphoplasmocytic index did not differ among themselves.

At the end of the same type of anticancer therapy in the analyzed indicator, patients have significant differences.

This lympho-monocytic index of 50 patients with cervical cancer Tsmgo stage, having in the next year after treatment verified relapse of the underlying disease, was significantly significantly lower compared with 55 patients, a similar prevalence of the process, but lived for 5 years after treatment without signs of recurrence of the underlying disease.

Examples of clinical application of the method.

1. Sick And 1958 birth, (ist. bol. No. 2314/d). The diagnosis of cervical cancer Tsmgo stage, endophytic form, vaginally-parametric option. Histogenesis No. 578 from 12.02.96 - squamous cell carcinoma without keratinization. Conducted combined radiation treatment in the form of remote gemmoterapii on AGAT-R and intracavitary With60therapy. Total focal dose at a reference point And 85 Gr, Netochka In 59,5 Gr.

Common blood test before treatment from 12.02.96

HB 130 g/l, er-4,2·l012/l CPU 0,92; lake.sphere-6,4·109/l as.-1%, and fell.-4%, segm.-52%, limp -27% (abs limp 1,73·109/l), mon 6%(abs. mon 0,38·109/l), erythrocyte sedimentation rate of 14 mm/hour. Lympho-monocytic index equal(1,73:0,38):4,05=1,12

General analysis of blood at the end of treatment 05.04.96.

HB 104 g/l, er -3,2·1012/l CPU 0,89; lake. - 3,7·109 /l as.-2%, and fell.-9%, segm. -69%, limp -17% (abs limp 0,62·109/l), MES 3% (abs. mon 0,11·109/l), erythrocyte sedimentation rate of 12 mm/h. Lympho-monocytic index equal(0,86:0,17):4,05=1,39

The patient is observed for 5 years with no signs of recurrence or metastasis of the disease.

2. Patient M, 1949 birth (East. bol. No. 5116/W). Diagnosed with cervical cancer TNxMo stage, endophytic form, vaginally-parametric option. Histogenesis No. 15303 from 30.07.98 - squamous cell carcinoma without keratinization. Conducted combined radiation treatment: remote gamma-therapy is recommended for the AGAT-R and intracavitary Soo therapy. Total focal dose at point a 82 G, point 57 Gr.

Common blood test before treatment from 31.07.98.

HB 96 g/l, er-4,0·l012/l CPU 0,82; lake.-4,4xl09/l as.-1%, and fell.-13%, segm.-55%, limp -26% (abs limp 1,14·109/l), mon 5%(abs. mon 0,22·109/l), erythrocyte sedimentation rate of 14 mm/hour. Lympho-monocytic index equal(1,14:0,22):4,05=1,27

General analysis of blood after treatment 05.10.98

HB 108 g/l, er-3,5·1012/l CPU 0,9; lake.-5,8·l09/l as.-9%, and fell.-7%, segm.-62%, limp -12% (abs limp 0,68·109/l), MES 10%(abs. mon 0,58·109/l), erythrocyte sedimentation rate of 24 mm/hour. Lympho-monocytic index equal(0,68:0,58):4,05=0,29

When appearing at the control examination after 6 months after treatment (05.04.99) vaginal scar adhesive process discovered small papillary growths, legkogruzovye when the dot is ugiwanie. Clinical diagnosis of recurrent cancer of the cervix. Condition after combined radiation therapy. Cytological study No. 13455 dated 05.04.99 - detected cells of squamous cell carcinoma.

Patient K., 1970 birth (East. bol. No. 9964/l). the diagnosis of cervical cancer Tsmgo stage, exophytic form, vaginally-parametric option. Histogenesis No. 42557 from 10.08.00 squamous cell carcinoma without keratinization.

Conducted combined radiation treatment: remote gamma-therapy device AGATE-R and intracavitary Soo therapy. Total focal dose at point a 80 Gr, point 54.6 G.

Common blood test before treatment from 10.08.00

Yves 108 g/l, er-4,2·l012/l CPU 0,92; lake.-4,7·109/l as.-3%, and fell.-11%, segm.-75%, limp -9% (abs limp 0,42·109/l), mon 2%(abs. mon 0,09·109/l), ESR 15 mm/hour. Lympho-monocytic index equal(0,42:0,09):4,05-1,15

General blood tests after treatment 12.10.00

HB 98 g/l, er-3,9·1012/l CPU 0,9; lake.-6,0·109/l as.-2%, and fell.-6%, segm.-58%, limp -26% (abs limp 1,56·10/l), mon 8%(abs. mon 0,48·109/l), erythrocyte sedimentation rate of 14 mm/hour. Lympho-monocytic index equal(1,56:0,48):4,05=0,8

With a turnout of 15.01.01 complaints dragging pain in the lower abdomen on the right. Local status: vagina low adhesive process. Fabric with a clean, soft. Through the adhesive process of the vagina the cervix is not clearly outlined. When viewed through the rectum cervix the pilot, without pathological overgrowth. The uterus and appendages without features. In the parametric spaces on both sides of the dense scar tictacti.

Cytological examination of scraping tissue adhesive process from 16.01.01 - blood cells of a flat epithelium with dyskaryosis, with no signs of atypia. Tumor cells were not found.

Ultrasound of the pelvic organs from 16.01.01. the amount of cervical 28,9 cm3. The size of the uterus and appendages normal values. Symptoms of retroperitoneal lymph nodes are not detected.

General blood tests after treatment 16.01.01

HB 89 g/l, er-4,1·1012/l CPU 0,9; lake.-4,1·109/l as.-2%, and fell.-7%, segm.-64%, limp -20% (abs limp 0,82·109/l), MES 7%(abs. mon 0,28·l09/l), erythrocyte sedimentation rate of 4 mm/hour. Lympho-monocytic index equal(0,82:0,28):4,5=0,72

The diagnosis of cervical cancer TNxMo, CL gr. III. Condition after combined radiation treatment. Recommended anti-inflammatory treatment.

With a turnout of 13.08.01. Complaints of lower abdominal pain with swelling of the right lower limb. Local status: vagina low adhesive process, the cloth clean. The line of adhesive process without seals. Examination through the rectum. The cervix thick, without pathological seals. The uterus and appendages without features. In the parametric space left scar tictacti. To the right is defined by dense infiltration of fiber in the Suppl parametrial space between the walls of the pelvis, tenderness on examination.

ULTRASONIC research of organs of a small pelvis from 13.08.01 volume of the cervix 29.5 cm, uterus and appendages correspond to normative values. The right internal iliac artery lazerette enlarged lymph node up to 2.5 cm in diameter.

Clinical diagnosis of cervical cancer TNxMo CL gr. II. Condition after combined radiation treatment. Relapse in the parametric space to the right.

The recommended course of systemic chemotherapy platinum source drugs.

4. Patient S. born in 1960 (East. bol. No. 11092/l) diagnosis of cervical cancer TNxMo stage, mixed shape, vaginally-parametric option. Histogenesis No. 12335 21.08.00 from poorly differentiated squamous cell carcinoma.

Conducted combined radiation treatment: remote gamma-therapy device AGATE-R and intracavitary Soo therapy. Total focal dose at point a 82 G, at a point 56 Gr.

Common blood test before treatment from 22.08.00

HB 114 g/l, er-3,9·1012/l CPU 0,9; lake.-3,9·109/l as.-2%, and fell.-1%, segm.-67%, limp -26%, (abs limp 1,01·109/l), MES 4% (abs. mon 0,15·109/l) ESR 10 mm/hour. Lympho-monocytic index equal(1,01:0,15):4,05=1,6

General blood tests after treatment 24.10.00.

HB 105 g/l, er-3,9·1012CPU 0,9; Lake.-4,0·109/l as.-7%, and fell.-9%, segm.-63%, limp -11% (abs limp 0,44·109/l), MES 10% (abs mon 0,4· 109/l), erythrocyte sedimentation rate of 21 mm/h. Lympho-monocytic index equal(0,44:0,4):4,05=0,27

With a turnout of over 6 months complains of abdominal pain of moderate intensity, worse at night.

Local status from 18.03.01: vagina adhesive process. Fabric with a clean, soft. The cervix is not clearly outlined, thick consistency. The uterus and appendages without features. In the parametric spaces of dense scar tictacti.

UZ-research from 18.03.01: cervix displacement 30,4 cm3with multiple areas of calcification and hypoechoic areas. Lesions of the retroperitoneal lymph nodes were not identified. Conclusion signs of malignant growth is not found.

General analysis of blood from 19.03.01

HB 104 g/l, er-3,7·1012/l CPU 0,8; lake.is 6.2·109/l as.-1%, and fell.-9%, segm.-57%, limp-22% (abs limp 1,36·109/l), mon 11% (abs. mon 0,68·109/l), ESR 15 mm/hour. Lympho-monocytic index equal(1,36:0,68):4,05=0,49

Given the primary extent of the process (stage TNxMo), complaints of the patient, the absence of data normalization lympho-monocytic index from 24.10.00 at the end of primary treatment 0,27; 6 months after treatment 19.03.01 0,49 recommended preventive courses of chemotherapy platinum source drugs. Conducted 3 standard preventive chemotherapy courses.

With a turnout of 12 months after the end of the combined radiation therapy 24.09.01 no complaints. The local status of a patient meets clinical recovery. Clinical and laboratory evidence of relapse of the underlying disease is not available.

General analysis of blood from 25.09.01

Yves 96 g/l, er-3,9·1012/l CPU 0,9; lake.was 3.7·109/l as.-3%, and fell.-4%, segm.-51%, limp-34% (abs limp 1,26·l09/l, mon 8% (abs. mon 0,29·109/l), ESR 15 mm/hour. Lympho-monocytic index equal(1,26:0,29):4,05=1,06

Technical and economic efficiency “a predictor of early recurrence and/or metastasis of cervical cancer” is that based on the evaluation values of lympho-monocytic index in peripheral blood at the end of the combined radiation treatment carry out early diagnosis continued tumor growth. The obtained predictive values of prognostic index allows to navigate in the true results of treatment individually to each patient. Offer lympho-monocytic index, which is a criterion for predicting the future course of malignant process cervical cancer TNxMo stage, opens the possibility to predict relapse before the manifestation of clinical symptoms and promptly appoint additional therapeutic benefits in controversial clinical si the situations. The calculation method is simple and can be easily implemented in any institution of practical health care.

A method for predicting early recurrence and/or metastasis of cervical cancer characterized in that at the end of concomitant radiotherapy determine the ratio of the absolute number of peripheral blood lymphocytes to the absolute number of monocytes in peripheral blood and divide by 4,05, when the values of the result above one imply the absence of the probability of developing cancer recurrence within the first year after treatment, while values below one predict the development of cancer recurrence in the first year after treatment.



 

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