[Radiotherapy as a component of treatment for Ewing's sarcoma].

The main stages of development of such conservative modalities as radio- and chemoradiotherapy for localized Ewing's sarcoma are discussed. Factors affecting five-year overall and recurrence-free survival of patients treated with chemoradiotherapy are presented.

[Osteosarcoma: biochemical and endocrinological studies as a basis for its pathogenetic treatments]. / Biokhimicheskie i éndokrinologicheskie issledovaniia pri osteosarkome -- osnova patogeneticheskikh metodov lecheniia opukholi.

The paper considers data of the long-term studies of androgen metabolism, baseline serum levels of reproductive steroid hormones and their receptors in the tumor, in the blood concentrations of sex steroid-binding globulin and pituitary hormones, the expression of epidermal growth factor, its receptors and ligands, soluble Fas-antigen, vascular endothelial growth factor, angiogenin, and the content of calmodulin, cAMP in the osteosarcoma in 300 patients aged 14 to 56 years, which were made at the N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. Analyzing the findings identified some lines in the study of new pathogenetic treatments for osteosarcoma, aimed at regulating androgen metabolism, correcting the cyclooxygenase pathway of arachidonic acid, the expression of receptors of epidermal growth factor and its ligands, the processes of neoangiogenesis in the tumor. A role of the above parameters in the pathogenesis of osteosarcoma is discussed.

[Sex and pituitary hormone secretion in normal-height and tall adolescents with primary osteogenic sarcoma]. / Sekretsiia polovykh i gipofizarnykh gormonov u normoroslykh i vysokoroslykh podrostkov, bol'nykh pervichnoi osteogennoi sarkomoi.

The paper deals with a comparison of basal levels of secretion of total testosterone (T) and estradiol-17 beta (E2), their free and albumin and sex-steroid-binding globulin fractions as well as LH, FSH, prolactin and STH in blood serum of 60 normal height and 60 tall healthy adolescents and those with primary osteogenic sarcoma of bones at different stages of puberty. The study established a significantly higher level of testosterone and free androgen index and a lowered concentration of sex-steroid-binding globulin in blood serum of both normal and tall adolescent patients with osteogenic sarcoma at different stages of puberty. No significant differences were found in said indexes of estrogens between sarcoma patients and a specific group chosen for comparison, as far as physical status is concerned. The role of sex steroid hormones and, particularly, that of androgens in the pathogenetical mechanisms of osteogenic sarcoma growth is discussed.

[The characteristics of eicosanoid synthesis in osteogenic sarcoma in children at puberty]. / Osobennosti sinteza éikozanoidov v osteogennoi sarkome detei v pubertatnom periode.

Levels of prostaglandin E (PGE), prostaglandin F2 alpha, prostacyclin A2, thromboxan B2 and leucotriene B4 assayed radioimmunologically were compared in 42 samples of osteogenic sarcoma and 22 samples of benign tumors and tumor-like lesions from children at the pubertal period. In osteogenic sarcoma samples, PGE and prostaglandin F2 alpha levels were higher than those of thromboxan B2, prostacyclin A2 and leucotriene B4. Osteogenic sarcoma revealed higher levels of the eicosanoids as compared to benign tumors and tumor-like lesions of the bone. An inverse correlation was established between PGE level and time of dissemination of osteogenic sarcoma. The role of eicosanoids in the pathogenesis of growth and dissemination of osteogenic sarcoma is discussed. The use of non-steroid anti-inflammatory drugs in complex treatment of osteogenic sarcoma of children at the pubertal period is suggested.

[Polypeptide growth factors and their interrelation with hormones in the blood plasma of patients with primary bone tumors]. / Polipeptidnye faktory rosta i ikh vzaimosviaz' s gormonami v plazme krovi bol'nykh s pervichnymi opukholiami kostei.

A relationship between blood plasma levels of polypeptide growth factors and those of peptide and sex steroid hormones, as assayed radioimmunologically, was studied in 91 patients with bone tumors of various histology and 45 healthy donors. The levels of insulin-like growth factor (IGF-1) and somatotropic hormone were significantly higher in cases of chondrosarcoma and patients suffering osteogenic sarcoma in the late puberal period as compared to controls and cases of fibrous histiocytoma, giant-cell tumor, benign tumors and tumor-like lesions of the bone. The peak levels of IGF-1, somatotropic hormone and insulin were registered in osteogenic sarcoma patients who developed pulmonary metastases either in the course or after the completion of combined treatment. Somatostatin level was significantly lower in patients with osteogenic sarcoma aged 11-20 years as compared to healthy adolescents, the lowest level being observed in adolescents suffering osteogenic sarcoma with metastases to the lungs. No relationship was established between total testosterone level, on the one hand, and those of IGF-1 and epidermal growth factor, on the other. A reverse correlation was established between concentrations of IGF-1 and total estradiol. The role of polypeptide growth factor antagonists in combined treatment of bone sarcomas is discussed.

[The results of using high-dose methotrexate in treating osteogenic sarcoma]. / Rezul'taty primeneniia vysokikh doz metotreksata pri lechenii otseogennoi sarkomy.

The interim results of the use of high-dose methotrexate with leucovorin rescue for the treatment of 26 patients with osteogenic sarcoma are discussed. Preoperative chemotherapy was followed by marked regression of primary tumor in one out of seven patients with localized disease. In that group, metastasis-free period lasted 2, 3, 10+, 12, 17+ and 24+ months. Response was observed in two out of 19 (10.6%) cases of metastases. Toxic side-effects were moderate and were mainly nausea (38.5% of patients), vomiting (26.9%), elevation of serum transaminase levels (38.5%) and fever (30.7% of cases).

[Clear-cell chondrosarcoma of bone]. / Svetlokletochnaia khondrosarkoma kosti.

Clinico-roentgeno-morphological characteristics of clear-cell chondrosarcoma are presented. Tumour cells had an abundant clear cytoplasm limited by a well discernible membrane; there were few giant multinuclear cells of the osteoclast type, zones of secondary osteogenesis and calcification. The lobulation of the structure was much less pronounced and the lobules were smaller and no so distinct as compared to an ordinary chondrosarcoma. All patients survived without recurrences and metastases after the operation.

[Steroid hormone receptors in osteogenic sarcomas]. / Issledovanie retseptorov steroidnykh gormonov v osteogennykh sarkomakh.

The method of hormone-receptor complex precipitation with protamine sulfate was used in 57 males suffering osteogenic sarcoma to identify and evaluate cytoplasmic androgen (AR) and estrogen receptor (ER) levels versus age and prior treatment as well as to assess their prognostic significance. AR were most often observed in younger patients and those pretreated with chemo- and radiotherapy whereas ER mostly occurred in older ones. Presence of AR (in untreated tumor or following preoperative therapy) adversely influenced prognosis. It took AR-positive tumors less time to disseminate to the lung after the start of treatment. The use of antiandrogen drugs for osteogenic sarcoma treatment is discussed.

[Clinico-morphologic characterization of lung metastases from osteogenic sarcoma during chemotherapy]. / Kliniko-morfologicheskaia kharakteristika legochnykh metastazov osteogennoi sarkomy pri khimioterapii.

Clinical and morphological characterization of osteogenic sarcoma (OS) and its lung metastases is presented in 16 patients, of whom 7 have not received preoperational chemotherapy. The morphological structures of the primary tumor and its metastases are shown to be of the same type. In most observations, OS metastases have been found to have no signs of therapeutic pathomorphism and their structures are identical to those of anaplastic polymorphocellular sarcoma with osteoid. The average life span of the patients was 35 months after pulmonary metastases removal.

[The relationship between the prostaglandin E level in the tumor and the times of the metastasis of primary osteogenic sarcoma]. / Sviaz' mezhdu urovnem prostaglandinov E v opukholi i srokami metastazirovaniia pervichnoi osteogennoi sarkomy.

Radioimmunoassay was used in 46 cases of osteogenic sarcoma to assess prostaglandin E (PgE) levels in tumor tissue. Those levels were found to vary with age. A correlation was established between the effect of preoperative chemoradiation treatment, on the one hand, and degree of treatment-induced pathomorphosis and PgE concentration in tumor, on the other. High PgE level in osteogenic sarcoma tissue proved prognostically unfavorable whatever age and prior chemoradiation treatment and were associated with shorter metastasis-free survival.

[Experience with and outlook for the use of cisplatin in the combined therapy of osteogenic sarcoma]. / Opy primeneniia i perspektivy ispol'zovaniia tsis-platina v kombinirovannoi terapii osteogennoi sarkomy.

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.

[Cytoplasmatic androgen receptors in malignant bone neoplasms and their relation to the morphological characteristics of the tumor]. / Tsitoplazmaticheskie retseptory androgenov v zlokachestvennykh novoobrazovaniiakh kostei i ikh vzaimosviaz' s morfologicheskoi kharakteristikoi opukholi.

"Free" and "total" (the sum of the occupied and free sites of binding) androgen receptors (AR) in the cytosolic fraction of 51 bone tumors were studied with reference to their histologic structure and treatment. "Free" AR were found in chondrosarcomas and osteogenic sarcomas previously treated two times more frequently than in untreated tumors. It is found that in untreated osteogenic sarcomas much more "total" AR in the cytoplasm are occupied with an endogenic androgen than in the treated tumors. More than a half of "total" AR in the cytoplasm of chondrosarcomas are bound with an endogenic androgen. The authors believe chondrosarcomas and osteogenic sarcomas treated with radiation and adriamycin to be more susceptible to the androgens than untreated osteogenic sarcomas. The evaluation of the susceptibility to the androgens of bone tumors which are followed or possibly stipulated by the metabolic disturbances of sex steroid hormones will be of value in the study of bone tumor hormonal regulation.

[Therapy and prognosis in Ewing's sarcoma]. / Terapiia i prognoz pri sarkome Iuinga.

The results of treatment of 134 cases of morphologically-verified localized Ewing's sarcoma were evaluated. A comparative analysis showed relapse-free survival to be significantly lower for radiation treatment (23%) than for its combination with various cytostatic drugs. Two-year relapse-free survival rate was as high as 43% in cases receiving sarcolysin or cyclophosphamide as adjuvants. This was matched by 47% for adjuvant adriamycin or carminomycin and 56% for adriamycin plus cyclophosphamide and vincristine. Evaluation of long-term results of adjuvant chemotherapy showed sex, age and site of involvement to be of certain prognostic value.

[Survival and prognosis in adjuvant chemotherapy for osteogenic sarcoma patients]. / Vyzhivaemost' i prognoz v usloviiakh ad"iuvantnoi khimioterapii u bol'nykh osteogennoi sarkomoi.

The effect of adjuvant chemotherapy on survival and prognosis in osteogenic sarcoma versus basic clinico-roentgenomorphological characteristics of tumor was studied in 108 cases. Prognosis was found to depend on patient's age, site and size of tumor, but mainly on the roentgeno-morphological pattern of the latter. Osteolytic form appeared to have a better course in cases of adjuvant chemotherapy. This was matched by osteoplastic form requiring surgical treatment only. The results suggest a strictly differentiated approach to selection of treatment modality, particularly in cases of post-operative chemotherapy.

[Role and place of radio- and chemotherapy in treating bone sarcomas]. / Rol' i mesto luchevoi i khimioterapii v lechenii sarkom kostei.

The results of combination therapy of 510 patients with osteosarcoma were analysed. It was established that most advantage is offered by this therapy in cases of osteogenic sarcoma and Ewing's sarcoma supplemented with surgery whenever required. A 33.9 and 30.1% increases in 3- and 6-year survival, respectively, were registered in 50 cases of osteogenic sarcoma, following amputation and a course of polychemotherapy (adriamycin, vincristin, sarcolysin and cyclophosphamide). There were no relapses in 40 cases of extensive segmental resection of the site of bone lesion with preoperative intra-arterial infusion of adriamycin, radiation therapy and adjuvant polychemotherapy. This scheme resulted in 4-year survival in 55.7% and good performance. A 5-year survival rose to 40.8% in 45 cases of Ewing's sarcoma, following adjuvant therapy with sarcolysin or cyclophosphamide administered after a course of radiation therapy in the dose of 50-60 Gy.