Method for predicting extracranial metastases development in patients having metastases in brain

IPC classes for russian patent Method for predicting extracranial metastases development in patients having metastases in brain (RU 2297005):

G01N33/74 - involving hormones

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FIELD: medicine.

SUBSTANCE: method involves determining adrenal glands cortex hormone cortisol content in blood. At its level below the bottom border of the norm making from 260.0 up to 450.0 nmole/l, within the limits of cortisol concentration fluctuations from 70.0 to 240.0 nmole/l, extracranial metastases development are predicted to occur in 1-3.5 months after primary examination.

EFFECT: high accuracy of prediction; enhanced effectiveness of treatment.

1 tbl

The invention relates to medicine, namely to biochemical research in Oncology, and can be used to predict the occurrence of metastases in internal organs and tissues in cancer patients with metastatic lesions of the brain.

When developing complex and sequence of therapeutic interventions in patients with metastatic brain disease that developed after radical treatment regarding the primary tumor, the important point are the results of a comprehensive examination of patients, aimed at assessing the state of internal organs and the incidence of metastasis. While feasible in terms of increasing the effectiveness of the treatment would be the ability to not only identify existing extracranial metastases, and prognosis of their development in the near term. This explains the urgency of the search for similar predictors of metastatic process among relatively quickly-defined parameters of blood for their implementation in clinical practice.

There is a method of diagnosing cancer using the definition in the blood of patients content of free polyamine is spermidine, spermine and putrescine (balicka O.V., Berlin NICHOLAS, N. Kononenko of Matters. on Oncology., 1992, V. 38, No. 6, S). Polyamine are growth factors, play a significant role in the processes of proliferation is cell differentiation. When tumor growth is one of the earliest metabolic events is a violation of metabolic processes associated with the transformation of polyamines. This is supplemented by an intense release from cells in biological fluids (blood, urine), where the concentration in this regard is greatly increased. On this basis, the authors determined the content of free polyamines in plasma and formed elements of blood in patients with nephroblastoma before and after treatment. The background concentration of spermidine, spermine and putrescine were above normal uniform elements of blood in 92,4% of cases, plasma - in 63% of cases. After surgical removal of tumors in 58% of patients the content of polyamines reduced. Their subsequent dynamics at different time points after primary treatment correlated with the efficiency of antitumor activities and individual characteristics of the disease. These results indicate that elevated levels of polyamines is possible to control the presence of tumor in the body, but the definition does not provide prospective information about the future direction of development of the disease. These figures cannot be used as a predictor of further spread of the metastatic process.

There is a method of evaluating the degree of teaching the tumor process in malignant tumors of the gastrointestinal tract (calini AV, Starlings SV Grew. W. Gastroenterol., gepatol., coloproctol., 1996, Vol.6, No.1, P.32). This method is chosen as a prototype. The authors propose to use to determine the prevalence of malignant process in patients with gastric cancer, pancreatic cancer, extrahepatic bile duct cancer and cancer of the colon definition in the serum content of several tumor markers - carbohydrate antigen 19-9 (CA-19-9), cancer-embryonic antigen (CEA) and α-fetoprotein (AFP). Determining the blood levels of these tumor markers, the authors found that CA-19-9 and CEA, with a fairly significant percentage of specificity can be used in the differential diagnosis of localized and generalized forms of these diseases. AFP is useful for the detection of liver metastases in patients with cancer of the pancreas and extrahepatic bile ducts.

The offered method of estimating prevalence of malignant process involves defining the content in the blood of several indicators, which increases the complexity and cost of the research. In addition to this factor, the above method is designed to assess the prevalence of disease and the presence of metastases in organs of the digestive system and cannot be informati the tion as a predictor of the development of foci of metastasis in other organs.

The state of the glucocorticoid function of the adrenal cortex determines adaptive capacity of the organism in norm and pathologies. On the other hand, the development of the malignant process in turn affects the body's systemic effect, including the effect on the functional status of various endocrine structures, including carisoprodolbuy activity of the adrenal glands. This justifies the search for a universal biochemical parameters, the dynamics of which in the blood was associated with the emergence and development of metastases in various organs and tissues and could be used as an additional laboratory test when assessing the clinical status of the patients.

The aim of the invention is forecast to clinical manifestations of the emergence of extracranial metastasis in various organs and tissues in cancer patients with metastases in the brain.

This objective is achieved in that in patients with metastatic brain lesion before treatment to determine blood hormone of the adrenal cortex cortisol and when its level is below the lower limit of normal, component from 260,0 to 450,0 nmol/l, within the fluctuations of concentrations from 70,0 to 240,0 nmol/l predict the development of extracranial metastases in 1-3,5 months after p is vicinage survey.

"A method for predicting the development of extracranial metastases in patients with metastases in the brain" is as follows.

We observed 3 patients with metastatic disease of the brain that evolved at different times after radical treatment of the primary tumor (breast cancer, lung cancer or melanoma). Prior to the treatment of brain metastases in patients was determined blood levels of adrenal cortex hormone cortisol. The determination was performed by standard radioimmunoassay method using standard test kits Cis bio International (France).

Analysis of the obtained data showed that patients with metastases in the Central nervous system the content of cortisol in the blood is significantly reduced compared with healthy people, and does not reach even the lower limit of normal physiological fluctuations of its level components 260,0-450,0 nmol/l (table). During the subsequent monitoring of patients, it was found that through 1-3,5 months, they have developed metastases in other organs and tissues (liver, lungs, bones, lymph nodes). Thus, the data presented indicate that low (to the lower limits of physiological norm) the content of cortisol in the blood of patients with metastasis to the brain is predictivity in the near future also metastases in other organs. This allows to consider the determination of the level of cortisol in the blood during the initial examination of patients with this cancer as an important informative laboratory test on the emergence and clinical manifestation in the near future metastases in other organs. Such information is obtained on delacerna stage should be taken into account when developing individual treatment tactics for patients with this cancer.

Table
The content of cortisol and the emergence of extracranial metastases in patients with metastatic brain disease
	Cortisol (nmol/l)	Detection of extracranial metastases
Healthy	342,31±17,96 (fluctuations from 260,0 to 450,0)
Sick
1	240,0	1.5 months
2	70,0	after 1 month
3	70,0	after 3.5 months

The specific examples of the application of the Method for predicting the development of extracranial metastases in patients with metastases in the brain".

CL is technical example No. 1.

Patient C-Ko B.C., born in 1948, case history No. 20182/R.

He enrolled in the Department of neurosurgery, RNII 9.12.2004, with a diagnosis of disseminated melanoma of the scalp, pT4N1M1, with metastatic lesions of the right frontal and parieto-temporal regions of the brain, stage IV.

Further examination in the hospital (ultrasound abdomen, CT of the chest) did not reveal the patient the presence of extracranial metastatic lesions in other organs.

Before spetslechenie 10.12.2004, the patient study of cortisol in the blood, which was 70,0 nmol/L.

Thus, the patient was identified low levels of cortisol in the blood, in the absence of the patient's symptomatic extracranial metastatic lesions.

13.12.2004, started the system of drug treatment on the method developed by us. Treatment endured quite well.

When re-entering 27.01.2005, in the neurological status of the patient without the negative dynamics, General - exhausted, lost weight, increase body temperature to 38.5°C. deterioration in General health status of the patient it has been re-examined.

When CT examination of the chest from 28.01.2005, revealed the presence of multiple metastases in both lungs and agenie mediastinal lymph nodes.

Thus, a low concentration of cortisol (70,0 nmol/l) were detected in the patient for 1.5 months before the clinical manifestation of multiple extracranial metastases and their confirmation on CT examination.

Technical and economic efficiency "method of forecasting the development of extracranial metastases in patients with metastases in the brain" is that the forecast of development of extracranial metastases in the near term prior to their clinical manifestations allows to develop and implement individual treatment of patients with metastatic brain damage. This method is highly informative laboratory test, quickly doable budget. Its application improves the effectiveness of treatment.

A method for predicting the development of extracranial metastases in patients with metastases in the brain, including biochemical, characterized in that in patients with metastases in the brain before treatment to determine blood hormone of the adrenal cortex cortisol and when its level is below the lower limit of normal, component from 260,0 to 450,0 nmol/l, within the fluctuations in concentration from 70,0 to 240,0 nmol/l predict the development of extracranial metastases in 1-3,5 months after the initial survey.</>