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MODERN METHODS OF CHILDHOOD CANCER MANAGEMENT
TENGIZ ZUKHBAIA, TBILISI, 2001This Book was written with the support of
The
National Association of Cancer Control ©
According to the latest data, the incidence of oncological diseases in children shows tendency to increasing. The range of these diseases is broad and by clinical course and results of special treatment they radically differ from the pathologies of the same type in adults.
In the first instance, it must be noted that it is inadmissible to perceive these patients as "Little Man" with malignant tumor.
The presented work deals with the treatment results of 174 children with different oncological diseases, using modern methods of diagnosis and special therapy. Of them malignant lymphoma was diagnosed in 23%, urogenital tumors - in 51%, tumors of bone and soft tissue - in 12%, neoplasm of nervous system - in 14% of patients.
Morphological verification (by cytology or histology) of clinical diagnosis was done in almost all cases. Ultrasonogpaphy as non-invasive and safe technique was used in most cases.
Computed tomography and magnetic resonance imaging was found to be helpful in providing exhaustive information on tumor spread (staging) and localization.
In the period of diagnosis and special treatment all patients were monitored using blood serum enzymoimmunoassay on different tumor markers.
Special treatment for oncological diseases in children is often with combined or complex methods of therapy including surgery, chemotherapy and radiotherapy.
Lymphosarcoma and lymohogranulomatosis are united under the same name - malignant lymphomas, but difference between them is very remarkable.
It must be noted that 90% of mediastinal lymphosarcomas are of lymphoblastic type. In such cases expression of neuronspecific enolase of tumor markers is highest (148,7±10.46 Ng/ml (norm - 14,28 Ng/ml).
Extranodal forms of lymphosarcoma are malignancies of special ethiology with cure rate of 90%. NSE concentration in these patients is correspondingly much lower - 44,33±8,25 Ng/ml.
These tumor markers are also helpful in determining tumor activity. In particular, in the patients of I degree risk group NSE<100 Ng/ml, whereas in those of III degree risk group NSE>100 Ng/ml.
Biological resources of extranodal forms of lymphosarcoma, even after applying primary radical surgery, are of great vitality, which can be suppressed by providing multiagent chemotherapy of adequate volume.
The prognosis of the patients with lymphosarcoma primarily depends on localization, histological type and staging of the disease.
Out of morphological types of lymphogranulomatosis variants with lymphoid predominance and mixed-cellular type were most often diagnosed (in 53% and 41% of cases, respectively).
It has been established that mixed-cellular types are more aggressive than those with lymphoid predominance.
There is significant difference between the biological activity of the patients in low and high risk groups which were formed in accordance with the extent of tumor spread (I and II groups, respectively). In the patients of I group NSE expression is 69,8±9,5% Ng/ml, whereas in those of II group NSE>98,2±26,8 Ng/ml.
It has been ascertained that I group patients having lymphogranulomatosis of morphological type with lymphoid predominance are well treatable. NSE concentration in this contingent of the patients is lowest - 66,2±3,9 ng/ml. Notwithstanding low biological activity of lymphogranulomatosis median value of NSE concentration is elevated in such cases. Multi-agent chemotherapy and radiation therapy is principle treatment of the patients with lymphogranulomatosis.
Nephroblastoma (or Wilms tumor) in children was most often diagnosed in the age group of 0-6 years. Owing to the wide range of histological types differential diagnosis of nephroblastoma is difficult to make. In most cases Wilms tumor is usually diagnosed. Of all patients with nephroblastoma admitted to our clinic mesoblastic nephroma was diagnosed in only two, whereas morphological structure corresponding to Wilms tumor was found in the remainder 88,8%.
Excretory urography, ultrasonography, CT, and MRT, as highly informative techniques, can be used in diagnosing nephroblastoma.
Informative capacity of ultrasonography is high (in 91,4% of cases). Magnetic resonance imaging was found to be superior to other imaging modalities in diagnosing bilateral tumors and other pathologies, which are difficult to identify, and in its ability to provide angiograpgic data (in 97,4% of cases).
Unlike other nosologies, in the patients with Wilms tumor high expression sensitivity of some tumor markers was revealed. Particularly, CEA concentration was almost 4 times as high as its permissible limit (28,54±9,2 Ng/ml).
Median value of NSE expression was 43,15±5,4 Ng/ml. In the patients with stage II Wilms tumor concentration of this marker was much lower - 30,63±1,78 Ng/ml.
It has been established that the loss of biological activity in the patients with Wilms tumor after surgery was not remarkable (NSE - 29,05±3,78 ng/ml), but cytostatic therapy resulted in its complete oppression, manifested in the decrease of NSE concentration to as little as permissible limit.
Therapy for infants is surgery only. In the patients with stage III Wilms tumor neoadjuvant cytostatic treatment should be conducted. In the same group of patients surgery should be followed by radiation therapy not later than 10 days after operation.
Standard multi-agent chemotherapy includes drugs: vincristine, cyclophosphane, dactinomycin, adriablastine, ifosfamide etc.
The use of up-to-date methods of diagnosis and therapy give us opportunity to achieve absolute cure in 80% of patients.
Malignant tumors of testis are most frequently diagnosed in the patients of age group bellow 3 years. Seminoma - most common pathology in the adults - is rare in children (most often is detected in the ages over 10 years). Embrionic rabdomiosarcoma and teratocarcinoma are most common non-herminogenic tumors in children.
During diagnosis and monitoring of the disease series serum enzymoimmunoassay on tumor markers has to be done. In the patients with enbryonal carcinoma AFP and NSE levels were elevated (80% and 61,95±0,34 Ng/ml, respectively), in those with leydigoma CHG and 17-ketosteriods expression was also high.
Surgery is standard treatment for achieving absolute cure in the infants. In the patients of age range 1-3 year prophilaxic radiation therapy (20-30 Grey) should be given to the paraaortal area. Our experience suggests that treatment of such type is absolutely equivalent to surgery - lymphadenectomy.
Multi-agent chemotherapy is widely used. Components and regimens of chemotherapy applied are determined by histological type and staging of the disease. Remote results depend on the patient's age, as well as histological type and stage of the tumor.
In 84% of embryonal carcinoma absolute cure can be achieved. 5-year and more survival of the patients with stage II and stage III embrional carcinoma is 90% and 18%, respectively. Complete recovery was achieved in 90,9% of the patients within 1-2 years.
Bone malignant tumors are characterized by particularly pronounced aggressiveness. Age-specific study revealed age range over 10 years having dramatically higher morbidity. In spite of high informative capacity of different radiodiagnostic methods, morphological examination is superior to them in its ability to provide differential diagnosis of the tumor.
Osteogenic sarcoma is usually managed by complex treatment. Neoadjuvant cytostatic or high dose radiation therapy is of significant importance.
It has been turned out that the high the rate of malignancy the predominant is NSE expression (89,0±25,2 Ng/ml). Special therapy applied resulted in significant decrease of this value. Lung metastases developed in average 4,6 months after special therapy.
Ewing's sarcoma is characterized by relatively lower biological activity and subsequent low concentration of NSE - 47,26±3,79 Ng/ml. Almost all patients admitted in our hospital had locally advanced and/or metastatic disease.
Malignant tumors of soft tissue are distinguished with complex histological structure and high rate of malignancy. In half of cases rhabdomyosarcoma was diagnosed.
Injury of orbit and extremities, as well as parameningeal and urogenital systems is very often detected (in 42%, 23% and 14% of cases, respectively). These diseases are usually managed by combined or complex therapy. Due to particular localization of these diseases, conduction of radical surgery is often impossible.
In order to assess the efficiency of special therapy and evaluate the possibility of developing residual tumor measurements of NSE and AFP concentrations have to be made during diagnosis. Concentration of NSE marker was 40,47±7,2 Ng/ml. At the same time in the patients with teratocarcinoma AFP expression was markedly evaluated - 200,0 V/ml.
Chemotherapy as well as radiotherapy is effective except for some histological types such as: fibrosarcoma, liposarcoma.
High biological activity of these diseases causes development of residual tumor within average 3,3-month period.
All oncological diseases in children are biologically high active, but neuroblastoma, as most aggressive it is, is characterized by clear evidence of different metabolic disorders which have subsequent negative influence on promote results. In 50% of the patients neuroblastoma was diagnosed in the age group bellow 3 years. Of them 60% has retroperitoneal localization. More over, 80% of the latter were inoperable. There exist many neuroblastoma-specific tests, but NSE measurement is most adequate procedure, which precisely determines degree of malignancy. NSE expression in the patients with neuroblastoma (129,78±27,25 Ng/ml) is as high as prognostic nondesirable limit (>100 Mg/ml).
Because of high aggressiveness of the disease combined therapy resulted in significant but temporary decrease of NSE expression - 36,33±3,0 Ng/ml.
A rapid extension of the disease interferes surgical treatment of the patients with neuroblastoma in most cases, but in those with mediastinal tumor conduction of surgery is possible.
Neuroblastoma most often was treated with multi-agent chemotherapy including different combinations of vincristine, cyclophosphane, adriablastine, platin, ifosfamide, vepezid, etc.
Radiation therapy is quite effective. Age of the patient, tumor localization and staging is of great importance in determining method and dosage of the therapy.
Progression of the disease manifested in developing metastasis in any organ is observed in 3 months after therapy. Metastatic tumor most commonly invades liver and skeletal bone - in 77% of patients. Lung and regional lymph nodes invasion is rare.
Tumors of brain have particular clinical course and biological activity. Medulloblastoma and ependymoblastoma are most frequent histological types, 46% and 30,7%, respectively. Magnetic resonance imaging is leading diagnostic method due to its high informative capacity (98% of cases).
In this contingent of the patients NSE expression is significant - 84,14±10,15 Ng/ml, independent of the value of surgical intervention and remains almost unchanged after radiation and other special therapy.
In our opinion, surgery is useful to achieve good treatment results in well-differentiated forms and special tophographic location of intracranial tumor. In general, despite multiple scientific researches, some aspects of physiology and path-physiology of the brain are insufficiently explored and require further investigations.
The study of tumor-associated markers becomes a problem of high priority. Our investigations suggest that concentration of NSE (neuron-specific enolaze of glycolysis enzyme) in blood serum is somewhat elevated in all cases. It must be noted that this marker is an adequate indicator determining biological activity of the disease. It is helpful in evaluating the rate of malignancy and in monitoring of the tumor, as well as in determining duration and value of adequate therapy. Thus, in our opinion, alternative schemes of therapy may be worked out and introduced to practice.
Most patients admitted to our clinic have advanced (stage III) disease, which had negative influence on survival rates.
The patients having tendency of developing different oncological diseases (children with congenital diseases, anomalies of different type, chromosome disorders, genitally loaded etc.) should be included in the risk group and long-term follow-up should be conducted. Prophylactic medical examinations include enzymoimmunoassay on different tumor markers, ultrasonography and other investigations 2-3 times a year. Such tactical approach guarantees early diagnosis of these diseases hence allows us to achieve best outcome.
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