IPC classes for russian patent Method for prediction of clinical outcome of chemoradiation therapy of squamous cell carcinoma of head and neck. RU patent 2505818. (RU 2505818):
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FIELD: medicine.
SUBSTANCE: immunoenzymometric analysis of blood serum TIMP-1 and TIMP-2 is combined with determining a primary tumour size according to the TNM classification, a degree of tumour differentiation, aging the patient and calculating a discriminant functions from the equations: Y1=-138.748+X1*15.963+X2*(-4.803)+X3*0.018+X4*2.319+X5*1.188 Y2=- 159.5454-X1*17.918+X2*(-4.266)+X3*0.028+X4*2.427+X5*1.242, wherein X1 is the primary tumour size according to the TNM classification, X2 is the degree of tumour differentiation, X3 is blood serum TIMP-1, ng/ml, X4 is a patient's age, years old; X5 is blood serum TIMP-2, ng/ml. If Y1>Y2, a high probability of the favourable outcome of the chemoradiation therapy is predicted. If Y1<Y2, a probability of no effect of the chemoradiation therapy is predicted.
EFFECT: more accurate, informative and effective treatment of the patients suffering malignant new growths of the head and neck.
2 ex
The invention relates to medicine, particularly to the Oncology and concerns to forecast the effectiveness of chemoradiation therapy () squamous carcinoma of head and neck.
There is a method of individual forecasting of treatment outcomes for patients with locally advanced common malignant tumors of oropharyngeal zone using the definition prior to treatment in the blood plasma of the patient of malonic dialdehyde (MDA): when set to MDA up to 5 units of optical density predict a favorable treatment outcome, at MDA from 5 to 8 units of optical density predict a satisfactory result of the treatment, and at MDA above 8 units of optical density predict an unfavorable outcome treatment [4].
Disadvantages of this method are:
- way in respect of the methods of treatment used for the treatment of malignant tumors of oropharyngeal zone that does not allow to assess the tactics of treatment of patients with the above localization of the tumor process.
The new technical task - increasing the accuracy and informative way.
To solve the problem in the way of predicting the effectiveness of chemoradiation therapy() accurate carcinoma of head and neck, including study of the level of TIMP-1 and TIMP-2 in the blood serum, further define the size primary tumor according to the international TNM classification, degree of differentiation of the tumor, age of the patient and expect to discriminate functions from the equations:
Y1=-138,748+X1*15,963+X2*(-4,803)+X3*0,018+X4*2,319+X5*1,188
Y2=-159,545+X1*17,918+X2*(-4,266)+X3*0,028+X4*2,427+X5*1,242, where
X1 - the size of the primary tumor according to the international classification TNM
X2 - the degree of tumor differentiation
X3 - serum level of TIMP-1 ng/ml
X4 - age of the patient, years;
X5 - serum level of TIMP-2 ng/ml
when Y1>Y2, we predict a high probability of a good outcome , Y1<Y2 forecast the probability of absence of the effect
New in the way of the forecast is used to assess the effectiveness of mathematical model, including the most informative indicators such as the level of tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 in the blood serum before treatment; size of the primary tumor (T-criterion of the TNM classification of malignant tumours); the degree of differentiation of the tumor and the age of the patient.
This approach to forecasting the efficiency of patients with malignant neoplasms of the head and neck is due to a number of premises:
- production of tumor number of metalloproteinases is connected with the formation mechanisms of radioresistance tumor tissue of [1, 3];
- high level of expression of TIMP-1 near tumors was associated with a poor response to chemotherapy [2].
The method is as follows. Spend study of blood serum of patients taken 1-2 days before the radiotherapy. Serum taken in a standard way, stored at -20 degrees, not more than 10 months. Serum samples defrost not more than 1 times for a study on the level of markers. Study of the level of TIMP-1 and TIMP-2 in the blood serum is carried out using sets for enzyme-linked immunosorbent assay for ELISA analyzer. determine the size of the primary tumor, according to the international TNM classification, degree of differentiation of the tumor, age of patient and expect to discriminate functions from the equations:
Y1=-138,748+X1*15,963+X2*(-4,803)+X3*0,018+X4*2,319+X5*1,188
Y2=-159,545+X1*17,918+X2*(-4,266)+X3*0,028+X4*2,427+X5*1,242, where
X1 - the size of the primary tumor, according to the international TNM classification
X2 - the degree of tumor differentiation
X3 - serum level of TIMP-1 ng/ml
X4 - age of the patient, years;
X5 - serum level of TIMP-2 ng/ml
when Y1>Y2, we predict a high probability of a good outcome , Y1<Y2 predict the probability of absence of the effect
The proposed method is based on the results of the analysis of clinical studies.
In the studied group consisted of 31 patients aged from 35 to 68 years (the average age was 53,5±1.3 years) with T2-4N0-2M0-stage disease who were treated in the Department of head and neck Oncology research Institute RAMS Siberian branch of confirmed malignant tumors of the larynx, pharynx and oral cavity bottom: morphologically all patients registered squamous cell cancer of various degree of differentiation. All patients received as an independent method of treatment. was performed using the 2 schemes: the first scheme (21 patients ) included 2 courses of chemotherapy (XT) on the scheme paclitaxel 175 mg/m2/ carboplatin - AUC-6, at intervals of 3-4 weeks. Then patients were LT. According to the second scheme (10 patients ) patients were LTL in standard mode in combination with 2 courses XT according to the scheme: paclitaxel 175 mg/m2/ carboplatin - AUC-6, interval between courses of 4 weeks. Results were evaluated by standard techniques and were defined as the full effect, a partial effect, stabilization or progression of cancer. Given that took part in an experiment patients treated on two protocols, the work was analyzed between background concentrations of inhibitors in the serum and treatment methods, as well as analyzed the effectiveness of the method of treatment, no significant differences in the compared groups were received, resulted in the further work to unite the patients receiving different ways in one study group.
During observation of the studied a group of patients the full effect from (regression of the tumor 100%) was registered in 8 patients, in 12 cases there was observed a partial regression of the tumor, the lack of effect of was observed in 11 patients with malignant tumors in the head and neck.
Held analysis, which resulted in the model presented two linear functions:
Y1=-138,748+X1*15,963+X2*(-4,803)+X3*0,018+X4*2,319+X5*1,188
Y2=-159,545+X1*17,918+X2*(-4,266)+X3*0,028+X4*2,427+X5*1,242, where X1 is the size of the primary tumor, according to the international TNM classification; X2 is the degree of tumor differentiation; X3 - serum level of TIMP-1 ng/ml; X4 - age of the patient, years; X5 - serum level of TIMP-2 ng/ml.
The sensitivity and specificity of the received model was 85% and 63%, diagnostic accuracy - 77%. When Y1>Y2 noted the presence of a high probability of a good effect , Y1<Y2 noted the presence of high-risk lack of effect .
Clinical examples:
Example 1. Patient N., 60 years old, was admitted to the Department HEAD of the Institute of Oncology in March 2006 with complaints about a hoarse, and sore throat. Considers himself to be ill during the year, the diagnosis is verified in the Bureau. Diagnosis: Cancer of the larynx T3N0M0. Histology: a highly differentiated squamous squamous cell carcinoma. Before treatment the patient took the blood to determine the level of TIMP-1 and TIMP-2 for forecasting chemoradiation treatment. Taking into account these indicators (TIMP-1=188,50 ng/ml (X3) and TIMP-2=88,70 ng/ml (X5), as well as the size of the primary tumor (X1=3), the degree of tumor differentiation (high) (x2=2) and age (60 years) (X4=60)were calculated discriminate functions:
Y1=-138,748+3*15,963+2*(-4,803)+188,5*0,018+60*2,319+88,695*1,188=122,0996
Y2=-159,545+3*17,918+2*(-4,266)+188,5*0,028+60*2,427+88,695*1,242=119,4554
As Y1>Y2, this patient is classified in the 1st group (with the alleged good effect chemoradiation treatment). Focusing on favorable prognosis patient was treatment as previously described. At a dose of 40 Gy efficiency of treatment was estimated as full regression. Radiation therapy is continued for up to SOD 66 . The patient was discharged in satisfactory condition is observed at the present, the total period of dynamic observation was 25 months.
Example 2. The patient,, 65 years old, was admitted to the Department HEAD in March 2008, complaining of ulcerative education on the lateral surface of the tongue. Ill since the summer of 2007, Diagnosis: Cancer language T2NOMO. Histology: squamous cell carcinoma, with a low degree of differentiation. Before treatment the patient took the blood to determine the level of TIMP-1 and TIMP-2 for forecasting chemoradiation treatment. Taking into account these indicators (TIMP-1=212,28 ng/ml (X3) and TIMP-2=106,84 ng/ml (X5), as well as the size of the primary tumor (X1=2), the degree of tumor differentiation (low) (x2=4) and age (65 years) (X4=65)were calculated discriminate functions:
Y1=-138,748+2*15,963+4*(-4,803)+212,28*0,018+65*2,319++106,84*1,188=155,448
Y2=-159,545+2*17,918+4*(-4,266)+212,28*0,028+65*2,427+106,84*1,242=155,6211
As Y1<Y2, this patient is classified in the 2nd group with the alleged bad effect chemoradiation treatment. Despite the poor prognosis in accordance with the Protocol to the patient held the instructions above. At a dose of 40 . estimated effect of the stabilization process. The effectiveness of treatment is regarded as a «bad effect». The second stage of the patient performed surgical intervention. The patient was released in satisfactory condition with a recommendation to be observed at the place of residence.
A method for predicting the effectiveness of chemoradiation therapy () squamous carcinoma of head and neck, including study of the level of TIMP-1 and TIMP-2 in the blood serum, wherein the further define the size of the primary tumor, according to the international TNM classification, degree of differentiation of the tumor, age of patient and expect to discriminate functions from the equations: Y1=-138,748+X1·15,963+X2·(-4,803)+X3·0,018+X4·2,319+X5·1,188 Y2=-159,545+X1·17,918+x2·(-4,266)+X3·0,028+X4·2,427+X5·1,242, where X1 is the size of the primary tumor according to international TNM classification; x2 is the degree of tumor differentiation; X3 - serum level of TIMP-1 ng/ml; X4 - age of the patient, years; X5 - serum level of TIMP-2 ng/ml; the Y1>Y2 predict a high probability of a good outcome , Y1<Y2 predict the probability of absence of the effect .
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