RU2299018C1 - Method for predicting the duration of relapse-free period in patients with serosal ovarian cancer - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: one should evaluate morphological parameters of tumor, moreover, the degree of tumor differentiation should be evaluated in points (X1): low degree of differentiation - 1 point; moderate - 2 points; high - 3 points. The nuclear area of cancer cell in sq. mcm (X2) should be measured with ocular-micrometer or analyzer of TV representation. Mitotic index (%0) (X3) should be determined due to calculating total quantity of division figures/1000 tumor cells. Specific portion of "lethal" mitotic forms against total quantity (%) (X4), the quantity of free cells/10000 mcm stromal area (X5), the density of vascularization (sq. mcm)/1000sq. mcm stromal area (X6) should be determined with analyzer of TV representation. The terms for the onset of relapse (Y) in mo should be determined according to the following formula: Y(mo)=(-30.42)-12,31*x1+0.04*x2-1.61*x3+1.41*x4+1.13*x5+1.29*x6. The present diagnostics enables to increase accuracy in detecting the duration of relapse-free period according to morphological characteristics of primary tumor.

EFFECT: higher accuracy.

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Description

The invention relates to medicine and is intended to assess the duration of a relapse-free period in treated patients with serous ovarian cancer.

The closest method is described in [1]. It consists in the fact that the time of onset of relapse in patients with breast cancer is determined by the value of the ratio of the concentration of total 17-hydroxycorticosteroids to the sum of the concentrations of cortisol, cortisone, tetrahydrocortisol, tetrahydrocortisone, established using a biochemical study in the patient’s urine. With a ratio ratio of less than 2.0, the duration of a relapse-free period of 3 to 6 years after the end of complex treatment is predicted, and with a ratio of more than 2.0, relapse develops up to 1.5 years after surgery.

The disadvantages of the method are the inability to use for ovarian cancer, the prognostic judgment is conditional, and the parameters used require specific biochemical methods.

The essence of the invention lies in the fact that the period of occurrence of relapse in months is calculated by the formula, which is a linear combination of several variables. The variables are the morphological parameters of the tumor.

The technical result of the invention is the high accuracy of determining the duration of a relapse-free period by the morphological characteristics of the primary tumor in patients with serous ovarian carcinoma and the possibility of using it in planning patient management tactics, as well as in choosing a treatment method.

The method is implemented as follows. Tumor parameters are determined such as the degree of histological differentiation, the area of the nucleus of the tumor cell, the mitotic index, the proportion of "lethal" forms of mitosis, the number of free stromal cells and the density of neoplasm vascularization.

The degree of differentiation of carcinoma is established in accordance with the criteria of A.C. Broders and is taken into account in points: low degree of differentiation 1 point; moderate - 2 points; high - 3 points.

The area of the nucleus of a cancer cell is measured by an eyepiece-micrometer or a television image analyzer in μm ² .

The mitotic index is determined by counting the total number of division patterns per 1000 tumor cells and is expressed in ppm (‰).

The specific fraction of “lethal” forms of mitoses for a cell is expressed as a percentage (%) of the total number of fission patterns.

The number of free cells is calculated per 10,000 μm ² stroma area using a television image analyzer.

The vascularization density is calculated by the analyzer of the television image per 1000 μm ² area of the stroma of the tumor and is expressed in μm ² .

Next, the period of occurrence of relapse (Y) in months is calculated by the formula:

Y (month) = (- 30.42) -12.31 · X1 + 0.04 · X2-1.61 · X3 + 1.41 · X4 + 1.13 · X5 + 1.29 · X6,

where X1 is the degree of tumor differentiation (1 - low, 3 - high);

X2 is the area of the nucleus of the cancer cell (μm ² );

X3 - mitotic index (‰);

X4 - specific proportion of lethal mitoses from the total number (%);

X5 - the number of free cells per 10000 μm ² stroma area;

X6 is the density of vascularization per 1000 μm ² stroma area (μm ² ).

The advantages of the method are the small number of used morphological criteria, the simplicity and low cost of the reagents to obtain the necessary parameters, the possibility of use in routine pathomorphological practice and medical science.

Examples of using:

1. Patient L., a pensioner, 62 years old, medical history No. 1525, was admitted to the Republican Clinical Oncology Center of Cheboksary on October 25, 1998 with complaints of drawing pains in the lower abdomen, an increase in the abdomen, and weakness. In the obstetric history of 10 pregnancies. Menopause for over 10 years. Objectively: the patient's condition is satisfactory, the skin is pale pink, hemodynamic parameters are within normal limits, vesicular respiration is in the lungs. On palpation, the abdomen was enlarged, soft, painless, with deep palpation, Obraztsov determined free fluid in the abdominal cavity. A vaginal examination revealed tumor formation in the pelvis up to 15 cm in size. There are no pathological discharge from the vagina. Cytological examination of ascitic fluid revealed atypical cells. No other changes in laboratory indicators have been established. With laparotomy, a tumor lesion of both ovaries of the cystic structure, metastatic lesion of the greater omentum were diagnosed. The uterus was extirpated with appendages and an omentum resection followed by 8 courses of chemotherapy and hormone therapy according to the standard scheme. Clinical diagnosis: Cancer of both ovaries, clinical stage III (FIGO), T ₃ N _x M ₀ , omentum metastasis, ascites.

A histological examination revealed a serous histological type of ovarian carcinoma with a high degree of histological differentiation (3 points). After a cytomorphometric study, it was found that the average area of the nucleus of the tumor cell is 22.7 μm ² . The mitotic index was 3.7 ‰, the specific fraction of mitotic forms of mitosis for the cell was 29%. In a morphometric study of the stromal component, the number of free cells per 10,000 μm ^{2 of} the stroma area was 8.84, and the vascularization density was 32.27 μm ² per 1000 μm ^{2 of} the stroma area.

Thus, we calculate the term for the resumption of tumor growth:

Y = (- 30.42) -12.31 · 3 + 0.04 · 22.7-1.61 · 3.7 + 1.41 · 29 + 1.13 · 8.84 + 1.29 · 32 , 27 = 20.1 months.

According to the follow-up of a patient received from an oncological clinic, it was found that relapse of a malignant neoplasm in patient L. developed 20 months after radical treatment.

2. Patient C., 58 years old, working, Case History No. 114, was admitted to the Republican Clinical Oncology Center of the Mountains. Cheboksary on August 27, 1997 with complaints of drawing pains in the lower abdomen, weakness. In the obstetric history of 2 pregnancies, menopause 5 years. Objectively: the patient's condition is satisfactory, the skin of the physiological color, hemodynamic parameters within normal limits, vesicular respiration in the lungs. On palpation, the abdomen is enlarged, soft, moderately painful in the left and right iliac regions. Free fluid in the abdominal cavity is determined. When a vaginal examination is diagnosed, tuberous tumor nodes in the pelvis up to 5 cm in size. Scanty spotting in the vagina. At a puncture of the Douglas space in the abdominal fluid revealed atypical cells. No other changes in laboratory indicators have been established. When laparotomy was diagnosed with a tumor lesion of both ovaries of a cystic-solid nature with a metastatic lesion of the omentum. The uterus was extirpated with appendages and gland resection followed by 4 courses of chemotherapy and hormone therapy according to the standard scheme. Clinical diagnosis: Cancer of both ovaries, clinical stage III (FIGO), T ₃ N ₀ M ₀ , ascites.

A histological examination revealed a serous histological type of ovarian carcinoma of a moderate degree of histological differentiation (2 points). Following cytomorphometric studies established that the mean area of tumor cell nuclei is 23.0 microns ^2. The mitotic index was 4.5 ‰, the specific proportion of mitotic forms of mitosis for the cell was 29.0%. In a morphometric study of the stromal component, the number of free cells per 10,000 μm ^{2 of} the stroma area was 6.05, and the vascularization density was 12.92 μm ² per 1000 μm ^{2 of} the stroma area.

Thus, we calculate the term for the resumption of tumor growth:

Y = (- 30.42) -12.31 · 2 + 0.04 · 23.0-1.61 · 4.5 + 1.41 · 29 + 1.13 · 6.05 + 1.29 · 12 , 92 = 3.02 months.

According to the follow-up of a patient received from an oncological clinic, it was found that a relapse of a malignant neoplasm in patient C. developed 3 months after the start of radical treatment.

The source of information

1. Patent of the Russian Federation No. 2251692, published May 10, 2005, Bulletin No. 13.

Claims (1)

A method for predicting the duration of a disease-free period in patients with serous ovarian cancer, characterized in that the morphological parameters of the tumor are evaluated: the degree of tumor differentiation in points (X1): with a low degree of differentiation - 1 point, with a moderate degree - 2 points, with a high - 3 points; the area of the nucleus of a cancer cell in μm ² (X2), measured by an eyepiece-micrometer or a television image analyzer; mitotic index (‰) (X3), determined by counting the total number of division patterns per 1000 tumor cells; the proportion of "lethal" forms of mitosis in the total number (%) (X4); the number of free cells per 10,000 microns of the stroma area (X5), determined by the television image analyzer; the vascularization density (μm ² ) per 1000 μm ^{2 of} the stroma area (X6), determined using a television image analyzer, and the period of occurrence of relapse (Y) in months is determined by the formula Y (month) = (- 30.42) -12.31 · X1 + 0.04 · X2-1.61 · X3 + 1.41 · X4 + 1.13 · X5 + 1.29 · X6.