[Treatment of relapsed osteosarcoma. Role of chemotherapy using ifosamide and carboplatin].

Our investigation involved 27 patients with osteosarcoma and 2--malignant fibrous histiocytoma of long tubular bones treated at the Center's Clinics (2001-2008). Two regimes were used for relapsed tumor: ifosamide up to 5-10 g/m2 (median 7.5) + carboplatin 300-750 mg/m2 (median 350) + etoposide 300-500 mg/m2 (median 450) (ICE), or doxorubicin 50-80 mg/m2 (median 60) (ICA). Surgical treatment used atypical resection of the lung or precision excision of metastasis. Median post-relapse follow-up was 18 months. When ICE was used, partial effect was reported in 3 (17.6%), stabilization--10 (58.8%), and tumor progression--4 (23.5%); ICA: partial effect--3 (25%), stabilization--6 (50%), tumor progression--3 (25%). Metastases were removed after a course of chemotherapy in 16 cases. Overall 3- and 5-year survival was 51.6 +/- 11% and 34.4 +/- 16%, respectively. Relatively more aggressive was the course of the disease in cases of early relapse (< or = 12 months), combination of local recurrence and distant metastasis and those who had not survived until a second surgical remission. Hence, timely combination therapy of relapsed high-grade osteosarcoma may secure relatively long remission in 35-40.3%.

Endostatin, placental growth factor, and fibroblast growth factors-1 and -2 in the sera of patients with primary osteosarcomas.

Serum levels of endostatin, placental growth factor (PlGF), and fibroblast growth factors-1 and -2 (FGF-1 and FGF-2) were measured in 58 patients with primary osteosarcomas before therapy and in 21 healthy subjects. The incidence of serum FGF-1 in bone tumors was 2.5 times higher than in healthy individuals (p=0.004); significant levels of FGF-2, PlGF, and endostatin were detected in all examined subjects. The mean serum level of endostatin in healthy individuals was significantly lower than in the total group of patients with bone tumors (p=0.005). The level of FGF-1 in osteosarcomas was significantly higher than in chondrosarcomas (p<0.05). No appreciable differences in FGF-2 levels were detected in patients with tumors of different histological structure. The mean serum content of PlGF was virtually the same in healthy individuals and patients with bone tumors. A significant relationship between serum PlGF level and maximum tumor size (p=0.008) was detected in osteosarcoma. No relationships between the levels of FGF-1, FGF-2, PlGF, and endostatin were detected in healthy subjects and patients with primary tumors of the bones. Differences in 3-year overall survival values of patients with bone sarcomas with different initial serum levels of FGF-1 and endostatin were detected.

[The role of clinical and imaging criteria in risk assessment during preoperative chemotherapy for osteosarcoma].

Prognosis for stage IIB osteosarcoma was evaluated versus the role of preoperative management of clinico-radiologic status in 293 patients. Three--five preoperative intra-arterial cycles of doxorubicin 90mg/m2 or cisplatin 120mg/m2 were given in 1986-1999, and later were followed by 3-4 cycles of doxorubicin and cisplatin in similar doses. Clinico-radiologic status was assessed in the course of preoperative chemotherapy. One hundred fifty patients were alive at the last examination, 139 had died of tumor progression, and 4 - chemotherapy complication. The two courses of preoperative chemotherapy were followed by more favorable outcome. Complete clinical response, tumors downsized to 300 mm, intra-osseous healing, periosteal assimilation and margination of extra-osseous masses had a significant positive impact on disease-free survival in the chemotherapy group. The data were used for the developing of models for individual risk evaluation and prognosis. Clinico-radiologic status monitoring in the course of preoperative chemotherapy is instrumental in predicting risks as well as designing alternative strategies of treatment at earlier stages.

[Thermoradiochemotherapy of inoperable soft-tissue sarcoma].

Three groups of patients with inoperable soft-tissue sarcoma received preoperative radiotherapy (57), thermoradiotherapy (102) and thermoradiochemotherapy (16) (n=175). Five year recurrence-free survival in group 1 was 37+/-7%, group 2 48+/-6%, and group 3 - 56+/-1,7%. Patients survived 5 years and more in group 3 (60+/-2%), group 2 - 50+/-7%, and group I 44+/-8% (p>0.05). Local hyperthermia used in conjunction with radio- and chemoradiotherapy was followed by a significant rise in the rate of complete and partial tumor regression.

[Treatment of limb osteosarcoma at the turn of the century (half century of experience in research)]. / Lechenie osteosarkomy konechnostei na rubezhe stoletii (poluvekovoi opyt issledovanii).

The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.