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A phase II trial of paclitaxel in the treatment of recurrent or metastatic soft tissue sarcomas or bone sarcomas.

The study aimed to determine the activity and toxicity of taxol in the treatment of recurrent or metastatic soft tissue sarcomas or osteosarcomas. The major findings are that five patients had stable disease after two cycles of chemotherapy but two of these patients were subsequently removed from the study at their own request. The other three patients progressed after an additional two cycles of chemotherapy. Seven patients progressed during the first two cycles and were removed from the study. One patient completed only one cycle of therapy and was deemed inevaluable for study response. There were eight episodes of grade 3 or 4 neutropenia and two episodes of grade 3 thrombocytopenia. One patient experienced grade 3 neurological toxicity and one patient grade 3 mucositis. Two patients are currently alive with progressing disease and one patient is alive with no evidence of disease after undergoing surgery and radiotherapy. The principal conclusions are that Paclitaxel is ineffective in treating recurrent or metastatic soft tissue sarcoma and osteosarcoma. Treatment at this dose is quite myelosuppressive, but toxicity is generally manageable. Further study of this agent is not justified in this setting.

Adult↗

[Surgical management of pulmonary metastases].

The results of surgical resection for pulmonary metastases from colorectal, breast, and renal cell carcinomas, soft tissue sarcoma, and osteosarcoma are reviewed. The number of pulmonary metastases, the presence of hilar or mediastinal involvement, and extrapulmonary foci are discussed in terms of surgical treatment. The size of pulmonary tumors or tumor doubling time has no significant effect on survival, while the number of metastatic foci does. Although a slight survival advantage has been noted for patients without hepatic metastases from colorectal cancer before pulmonary metastases occur, the difference in survival rates among patients with and without hepatic metastases is not significant. The role of surgery is less clear in breast cancer patients, and therefore further prospective study is considered essential. Higher relapse rates have been reported in patients with soft tissue sarcoma and osteosarcoma, although patients with these metastases can achieve long-term survival after a second metastasectomy. VATS is not be recommended for metastatic cancer surgery, because intraoperative identification of metastatic foci is often difficult.

Breast Neoplasms↗

[Indications for thoracotomy in pulmonary metastatic sarcoma and its prognosis].

Between 1960 and 1987, 46 patients underwent thoracotomy for pulmonary metastatic sarcoma. The histologic classification of the sarcoma was osteosarcoma in 33 patients, other malignant bone tumors in 6 and soft tissue sarcoma in 7. The cumulative five-year survival rate of the 33 patients with osteosarcoma was 23%. Ten patients survived more than 3 years and 8 of them are still alive without pulmonary metastasis. Prognosis was significantly better with intensive multidrug chemotherapy. In this series, prognosis was not significantly related to the interval from initial onset to initial treatment, that from initial treatment to pulmonary metastasis and that from pulmonary metastasis to initial thoracotomy. The five-year survival rate of the 6 patients with other malignant bone tumors was 35%, and that of the 7 patients with soft tissue sarcoma 26%. Good indications for thoracotomy in pulmonary metastatic osteosarcoma are: (1) the primary sarcoma is resected, (2) the interval from initial treatment to pulmonary metastases is more than 6 months, (3) the number of pulmonary metastases is less than 4 or 5 nodules, and (4) the number and diameter of pulmonary metastases is controlled with chemotherapy within 2 or 3 months after occurrence of metastasis.

Adolescent↗

[Efficacy and problems of radio- and chemo-combination therapy for malignant bone tumors].

In this study we reviewed cases of osteosarcoma, malignant lymphoma of bone and Ewing's sarcoma. Historically, osteosarcoma was unresponsive to chemotherapy. Most patients were treated by radiation or amputation alone and 80% of them died from pulmonary metastasis within 2 years. Five-year survival rate was 13%. Introduction of ADM, HD-MTX and CDDP improved dramatically the prognosis of these cases. Five-year survival rate was 60%. On the other hand, 11 cases of malignant lymphoma of bone and 4 cases of Ewing's sarcoma were treated by radiation with no local recurrence. VEPA or CHOP chemotherapy was used for the former with a five-year survival rate of 45%. For the latter, T-11 protocol (Rosen) was applied, and all patients survive with no metastasis. Other organ injuries circulatory disturbance, bone necrosis and growth-disturbance of bone in radiotherapy, myocardiopathy caused by ADM and renal toxicity of CDDP are all problematic.

Adolescent↗

The biology of human cells in tissue culture. I. Characterization of cells derived from osteogenic sarcomas.

We have extensively characterized cell lines derived from six human osteosarcomas. The growth properties of these cultures were compared to those of fibroblastic cultures derived from skin of osteosarcoma patients and skin of bone-marrow of normal individuals. Each tumor-derived line showed some but not all of the abnormal growth properties usually associated with malignant transformation, indicating that tumor cells rather than normal stromal cells had in fact been cultured. The parameters measured included saturation density, cell morphology, growth pattern, growth on contact inhibited monolayers of normal fibroblastic or epithelial cells and tumorigenicity in immunosuppressed mice. Although the skin fibroblasts from the osteosarcoma patients appeared normal in vitro, they showed a greater ability to grow in immunosuppressed mice than did normalfibroblasts. This observation suggests that all fibroblasts of osteosarcoma patients may have an increased propensity for malignant transformation.

Adolescent↗

[Immunological study in carcinogenesis. Distribution of tissue incompatibility antigens (system HL-A) in oncological patients].

By means of a micromethod of lymphocytotoxic test the content of eleven HL-A antigens (1, 2, 3, 5, 7, 8, 9, 10, 11, 12 and 13) was studied in 200 healthy human subjects, 100 patients with rheumatoid polyarthritis and 82 patients with bone tumors. The latter included 50 patients with benign tumors (osteoblastoclastomas, chondroblastomas, chondromas, non-osteogenic fibromas) and 32 patients with malignant tumors (chondro- and osteosarcomas, Ewing sarcoma, malignant osteoblastoclastomas). It was found that in patients with different bone tumors antigen HL-7 was encountered reliably more frequently than in control groups, in patients with malignant tumor also antigen HL-A10 was more often detected. The most frequently observed haplotyes in oncological patients were HL-A3/7 and HL-A2/7. In patients with rheumatoid polyarthritis antigen HL-A3 was found more rarely and antigen HL-A10 more frequently than in healthy subjects. The most frequent haplotypes in this group were as follows: HL-A2/7, HL-A2/8 and HL-A11/12. The possible mechanisms of the relationship between HL-A antigens and the development of pathology are discussed. Some considerations are offered concerning the possibility to utilize HL-A typing for an accessory differential diagnosis.

Arthritis, Rheumatoid↗

Xenografts in pharmacologically immunosuppressed mice as a model to test the chemotherapeutic sensitivity of human tumors.

A human tumor xenograft model using pharmacologically immunosuppressed mice was assessed for its suitability to test preclinically the sensitivity of colorectal carcinomas, bone sarcomas and melanomas against anticancer agents. Besides ionizing radiation, 14 cytotoxic drugs including 5-fluorouracil (5-FU), dimethylmyleran (DMM), cytosine arabinoside, cyclophosphamide, melphalan, BCNU, mitomycin C, adriamycin, bleomycin, etoposide, vinblastine, cisplatin, procarbazine and DTIC were assayed. Ionizing radiation, 5-FU and DMM were also applied at lethal doses followed by bone-marrow rescue heavy therapy. Four colon carcinomas responded poorly to most of the agents but one tumor displayed marked sensitivity to BCNU. Lethal doses of radiation, 5-FU and DMM could also show considerable activity. High sensitivity was shown by a Ewing sarcoma to DMM and cyclophosphamide and by an osteosarcoma to the latter drug. No strong effects were seen against melanomas. Lethal doses of DMM induced the best regression of one colon carcinoma. In general, the superiority of heavy therapy for solid human tumors compared to maximally tolerated doses was demonstrated. Individual carcinomas of the same type displayed different drug sensitivity.

Animals↗

Soft tissue sarcoma in adults.

Soft tissue sarcomas are a heterogeneous group of tumors, consisting of numerous histiotypes that all share a putative common mesenchymal origin. Although prognosis of these tumors is determined by clinical parameters (size, location, and resection margin status) and pathologic features (mitotic activity and necrosis), the histologic subtype has never been shown to be a consistent independent prognostic factor. Some relevant differences among these histiotypes are emerging, in specific biological parameters such as proliferation indices, in integrin expression profiles, and with regard to drug sensitivity. Several biological factors are considered to be prognostically important. Most attention is directed to regulators of cell-cycle progression. The significance of p53 dysregulation is confirmed by the inhibition of cellular proliferation, both in in-vitro and in in-vivo sarcoma models, after reintroduction of wild type p53. A multidisciplinary approach is essential for the optimal treatment of soft tissue sarcomas. Multimodality treatment has led to a patient-tailored approach with limb-sparing resections integrated with external and/or interstitial irradiation. The value of chemotherapy both in the neoadjuvant and the adjuvant setting, although of critical value in other sarcomas such as Ewing's sarcoma and osteosarcoma, remains to be established for soft tissue sarcomas.

Adult↗

Osteosarcoma and Ewing's sarcoma in a retinoblastoma patient.

Retinoblastoma, though uncommon, frequently is associated with other second malignant neoplasms, especially bone sarcomas. These second neoplasms can occur in sporadic cases of retinoblastoma, though they more commonly are associated with genetic forms of the disease. This is the first known report of 2 histologically distinct bone sarcomas in a patient with retinoblastoma.

Child↗

Incidence of anemia in children with solid tumors or Hodgkin disease.

Anemia is a hematologic abnormality commonly discussed during the treatment of childhood cancer, but its incidence has not been previously reported. As the basis for determining the incidence of anemia, this retrospective review of medical records combined databases containing the records of all patients 1 to 18 years of age with newly diagnosed neuroblastoma, rhabdomyosarcoma, Hodgkin disease, Ewing sarcoma, or osteosarcoma from two pediatric oncology centers. Data from 405 patients were included in the analysis of hemoglobin at the time of diagnosis. Across diagnoses, 51% to 74% of patients were anemic using the Centers for Disease Control and Prevention age- and sex-specific values to define anemia. The long-term complications of anemia in children with cancer are unknown. Further investigation of the clinical significance of anemia, including its impact on quality of life, is warranted.

Adolescent↗

Wide resection of primary tumors of bone and replacement with massive bone grafts: an improved technique for transplanting allogeneic bone grafts.

The treatment by wide resection of 104 local aggressive and low grade malignant bone tumors is presented with results after follow-up for 5.0 years on the average. The series comprises 29 giant cell tumors, most of them malignant or premalignant, 25 cartilaginous tumors (12 verified chondrosarcomas and 13 chondromas suspect of malignancy), 14 cases of sarcoma, 6 of fibrosarcoma, 4 parosseal sarcomas, 3 osteosarcomas and one chordoma. The remaining 36 cases include: aneurysmal bone cysts, fibrous dysplasia, chondroblastomas, osteoblastomas, giant chondromyxoid fibroma, and hemangiomas. After resection of the affected area, the resulting defect was replaced with massive autologous or allogeneic bone or osteoarticular graft in altogether 68 cases (autologous bone transplant in 61 cases and allograft in 7). A metallic endoprosthesis was used in replacement in 8 cases. No replacement of the defect was needed in 28 cases. The technique of the allogeneic bone transplantations consisted of massive bone or bone cartilage grafts which had been stored at a low temperature, and firm osteosynthesis. In every case, allogeneic (stored) bone was supplemented with autologous cancellous bone around the juncture of graft and host bone. This supplement proved to be important for success of the operation. The overall results were good in 81% and fair in 11%. Five cases had to be amputated and 3 patients were lost to follow-up, a possible total of 8% poor results. Extensive resection with massive bone grafting is a worthwhile approach in the treatment of selected cases of aggressive and low grade malignant bone tumors.

Adolescent↗

Bone sarcoma characteristics and distribution in beagles injected with radium-226.

A total of 155 primary bone sarcomas were found in 131 of the 246 beagles injected with 226Ra and 5 primary bone sarcomas were found in 4 of the 158 unexposed controls. Of these 155 bone sarcomas, 146 (94%) were osteosarcomas and 9 were non-osteosarcomas. An additional 31 primary bone sarcomas (28 osteosarcomas) developed in 44 dogs terminated from the main study because of limb amputation for bone sarcoma. Non-osteosarcomas predominated in both the controls and the second lowest of six logarithmically increasing dose levels (there were no bone sarcomas in the lowest dose group). Osteosarcomas predominated at the higher dose levels, and incidence tended to increase as dose increased. The 146 osteosarcomas were distributed quite evenly between males and females (72:74). Of the 9 non-osteosarcomas, 6 occurred in males and 3 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 110:45, with osteosarcomas occurring more often in the appendicular skeleton (108:38). Cases of multiple primary bone sarcomas in dogs injected with 226Ra were found only in the four highest dose groups. Amputations were performed on 44 of the 96 dogs (94 injected and 2 unexposed) that developed appendicular bone sarcomas. A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a statistically significant correlation to cancellous skeletal surface, but the variability among bone groups was too large for this relationship to be of real predictive value. It is postulated that the distribution of bone sarcomas reflects primarily the relative cell division rates in the bone groups and secondarily the radiation dose distribution, with the highest occurrence of bone sarcoma in the humeri, pelvis, femora and tibiae/fibular tarsal, and no occurrence in the coccygeal vertebrae, sternum, forepaws or hindpaws.

Animals↗

Sarcomas.

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Animals↗