Screening for germline p53 mutations in pediatric and adult patients of high-risk groups in Poland.

Germline mutations of the p53 gene lead to cell transformation in various tissues. Such a complex cancer phenotype makes it difficult to recognize the carriers of the defective allele. Several studies undertaken to identify high-risk groups found germline p53 mutations in familial cancer aggregations and in patients with multiple tumors. We screened 189 pediatric and 48 adult patients. The high-risk groups comprised 41 patients with a family history of cancer and 35 with multiple neoplasms. Furthermore, 124 tumors were screened for somatic mutations. p53 exons 2 to 11 were analyzed by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing of abnormal DNA fragments. No germline p53 mutations were found and somatic mutations were detected in 5 of 59 sarcomas, globally, in 8 of 124 tumors. In conclusion, in Poland, p53 alterations do not seem very important for the predisposition to malignancy and development of sarcomas.

[Progress in the treatment of 155 children with rhabdomyosarcoma obtained in one center between 1962-1990]. / Postep w leczeniu rhabdomyosarcoma uzyskany w jednym osrodku u 155 dzieci w latach 1962-1990.

The results of treating 155 children with rhabdomyosarcoma using protocols that (RMS) changing over the years between 1962-1990 in reported to progress in chemotherapy (CHT), introduction of megavoltage radiotherapy (RTX) and conservative surgery with attempts to preserve vital organs are presented. In the first period between 1962-1980 when mainly surgery was applied with orthovoltage RTX and low intensity CHT, only 20 of 74 children (27%) survived. In the second period 1981-1985 systemic CHT containing new cytostatic, megavoltage RTX and limited surgery applied in advanced cases after induction of CHT were introduced. Nineteen of 46 children (41.3%) survived. In the last period a 1986-1990 more intensive CHT with an own modified protocol VACA/VAIA and intensification phases containing cisplatinum, etoposide and/or carboplatinum were introduced. Twenty seven of 35 patients (60%) survived. Comparative analysis of the last two periods pointed to significant progress in treatment in III clinical group (IRS classification), (20.7% vs 62.9%) and parameningeal RMS (0% vs 58%). Meaningful improvement concerned also young children below 5 years of age (42.8% vs 73.9%). The main prognostic factors and treatment failures of the recent years were analyzed.

[Preliminary evaluation of individualized use of large doses of methotrexate for treatment of osteosarcoma in children and adolescents]. / Wstepna ocena zastosowania indywidualizowanych duzych dawek metotreksatu w leczeniu miesaka kosciopochodnego u dzieci i mlodziezy.

To improve the final treatment results in children with osteosarcoma, we applied after French DD-11 protocol HD MTX increasing with the younger age of patients, modified next on the basis of maximal serum drug concentrations (Cmax) as feed-back dosing. Toxic side effects were analysed according to WHO grading correlated with MTX elimination. We administered 39 HD MTX courses in 13 patients with osteosarcoma: aged 7-20 yrs (median 12 yrs). We performed 301 measurements of MTX concentration using the method of fluorescence polarisation. Therapeutic Cmax of 1000 microM/L and higher were obtained in 20 courses, the mean of lower values was 770 microM/L. We modified the next MTX doses in 23.7% of courses. Drug elimination was good in the majority of cases: in 34 of 39 courses at 24 hrs, in 36 of 39 at 48 hrs. Nevertheless, III and IV degree toxic side-effects accompanied about half of the courses and could not be predicted by MTX serum level measurements. HD MTX therapy with monitoring MTX serum levels proved feasible with acceptable toxicity. Therapeutic MTX levels were obtained in about 60% of cycles in patients with a favourable course of the disease in comparison with 25% in patients with an unfavorable course but the beneficial effect of age-tailored MTX and feed-back dosing on the treatment results will be possible to assess in the next 3 years.

[Methods used in the diagnosis and treatment of rhabdomyosarcoma]. / Analiza metod stosowanych w rozpoznawaniu i leczeniu nowotworów miesni poprzecznie prazkowanych.

The authors present their own clinical material of 74 cases of rhabdomyosarcoma in children, treated in the years 1962-1980. The analysis consists of generally used methods of diagnosis and treatment. Diagnosis was made on the base of clinical, radiological and pathological examination. Treatment was established after stagging qualification and after actually used methods. The treatment based on surgery, radiotherapy, and simple drug chemotherapy was giving bad prognosis and good results was obtained in single cases only. Significant improvement in the results was obtained after multidrug chemotherapy introduced into combined treatment (40%).

[Role of chemotherapy in the treatment of Wilms' tumor in children]. / Rola chemioterapii w leczeniu guza Wilmsa u dzieci.

In the years 1962-1976, 168 children with nephroblastoma (Wilms Tumour) were treated in the Clinical Department of Child Oncology of the Institute of Mother and Child in Warsaw. In 150 cases, independently from surgery and radiotherapy, chemotherapy was performed. Our material was divided into 5 groups: a) without chemotherapy, b) chemotherapy with different drugs, c) chemotherapy with 1 course of Actinomycine D, d) chemotherapy with several courses of Actinomycine D, e) chemotherapy according to SIOP Trial. The results with reccurency free survival are as follows: a) 22,2%, b) 24,1%, c) 28,1%, d) 46,6%, e) 56,6%. In our material the best results were received with SIOP Trial chemotherapy.

[The spinal cord compression syndrome in children with mediastinal neuroblastoma]. / Zespól ucisku rdzenia w neuroblastoma sródpiersia u dzieci.

The authors present 5 cases of mediastinal neuroblastoma in children with the syndrome of medullar compression. The problems of the diagnosis, the treatment and the prognosis are discussed. The attention is called to the rapidity of neurological signs progression and the diagnostic significance of cerebro-medullar fluid and radiological examinations (thoracic and vertebral X-rays and myelography). The necessity to decompression (laminectomy) as quick as possible is underlined. The authors indicate that these cases must be evaluated and treated in the complex way and the tumour advancement, neurological disorders, appropriate orthopedic supplies and rehabilitation must be considered respectively. The serious prognosis, especially in children above one year of life, is emphasized.

[Metastases of retinoblastomas to the bones of children]. / Przerzuty do kosci w retinoblastoma u dzieci.

The authors present their own clinical material of retinoblastoma in children treated in the Clinical Department of Child Oncology of the National Research Institute of Mother and Child in Warsaw, in the years 1962-1976. Analyses of epidemiological and clinical data of 47 cases was done, and a four-stage classification was established. Case report of bone metastases of retinoblastoma from material is presented with some conclusions concerning treatment and prognosis in cases with bone metastases.