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At least 91 records · Page 5Linked to original sources
PubMed1989

Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma. Cooperative Osteosarcoma Study Group COSS.

Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Tumors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.

Bone Neoplasms↗
PubMed1989

[Results of treatment in primary disseminated osteosarcoma. Analysis of the follow-up of patients in the cooperative osteosarcoma studies COSS-80 and COSS-82].

Since the long-term disease-free survival rate in adjuvantly treated osteosarcoma has nowadays reached a level of about 70%, increasing interest is also being directed towards primarily disseminated forms of the disease. Primary metastases, which were confined to the lungs in 42 cases, were detected in 59 out of 421 patients from the prospective therapy trials COSS-80 and COSS-82. The primary tumors were more frequently localized in the proximal femur and flat bones as compared to patients without detectable metastases at diagnosis. Following chemotherapy and surgery of the primary tumor, 15/31 (48%) patients whose metastases were excised have survived for 4-8 years, in contrast to only 1/22 (5%) of those patients whose metastases could not be removed for a variety of reasons. Clinical or histological evidence of tumor response after primary chemotherapy significantly influenced the outcome of the metastasectomized patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.

Adolescent↗
PubMed1983

Toxicity associated with combination chemotherapy for osteosarcoma: a report of the cooperative osteosarcoma study (COSS 80).

The treatment-associated toxicity in 189 patients entered in the COSS-80 Study was analyzed. The sequential use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and cis-platinum may be additive or synergistic in causing renal toxicity. However, evaluation of the 48-h serum methotrexate level and the incidence of elevated serum creatinine levels throughout treatment failed to indicate prolonged methotrexate elimination or severe kidney damage from this regimen where an interval of 3 weeks between cis-platinum administration and the next course of HDMTX was mandatory. The treatment-related mortality was 3.2% (6 out of 189 patients). Three patients died of septicemia during chemotherapy-induced bone-marrow depression following treatment with adriamycin or the combination of bleomycin, cyclophosphamide, and dactinomycin (BCD). Three deaths occurred following the use of high-dose methotrexate with citrovorum factor rescue. Two of these deaths were associated with delayed excretion of methotrexate. The toxicity is within the range reported in the literature.

Acute Kidney Injury↗
PubMed1989

Osteosarcoma and interferon. Studies of human xenografts in the nude mouse.

This work assessed the transplantability of human osteosarcomas to immunodeficient nude mice. Osteosarcomas serially transplanted in nude mice were characterized by growth rate, histologic features, and nuclear DNA content. The osteosarcoma xenografts were used to investigate the antitumor effects of interferon (IFN). Tumor tissue from 25 primary osteosarcomas was transplanted into nude mice. All tumors were histologically of high grade (III-IV). Flow DNA cytometry disclosed that all, except 1, had a nondiploid DNA content. 14 of the 25 osteosarcomas grew in serial passage in nude mice, i.e., the take rate was 0.6. The transplantable osteosarcoma group was characterized by a predominance of Grade IV lesions, and a high proportion of proliferating cells, compared to the nontransplantable. The 14 osteosarcoma xenografts, established in nude mice, were heterogeneous with respect to growth rate, histologic subtype, DNA content, and proliferative activity. However, the osteosarcomas retained the basic characteristics of their respective original tumor; the xenografts exhibited the same histologic appearance and DNA content in the first 2 passages in nude mice. During serial transplantation of the 14 osteosarcomas, the histologic features remained unaltered from passage to passage during the observation period of up to 3 years. The aneuploid DNA content was also unchanged over time in most tumors. However, in 4 osteosarcomas with 2 aneuploid cell populations, the cell population with the higher DNA content became predominant, while the other gradually disappeared. Hence, the changes in DNA content involved polyploidization, followed by selection of the cell population with higher DNA content. At the same time growth rate increased, but histologic features were unchanged. This study of osteosarcoma, serially transplanted in nude mice, shows that growth rate, histologic appearance, and DNA content are relatively stable tumor features. The observed changes in DNA content illustrate the development of aneuploidy in malignant tumors. The antitumor effects of human nIFN-alpha were assessed in the 14 osteosarcoma xenografts. In dose-response experiments, based on 2 different tumors, 2 x 10(5) IU/day of nIFN-alpha was found to arrest tumor growth. This dose was chosen as the standard dose in subsequent experiments. Among the 14 osteosarcomas, tumor regression or growth arrest was seen in 5, whereas 8 were only partially growth inhibited with the standard dose. The remaining osteosarcoma was growth inhibited with higher nIFN-alpha doses. Hence, all 14 analyzed osteosarcomas were sensitive to the antitumor effect of nIFN-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Comparisons of the skeletal locations of putative plutonium-induced osteosarcomas in humans with those in beagle dogs and with naturally occurring tumors in both species.

Osteosarcomas occur from exposures to bone-seeking, alpha-particle-emitting isotopes, particularly plutonium. The skeletal distribution of putative 239Pu-induced osteosarcomas reported in Mayak Metallurgical and Radiochemical Plutonium Plant workers is compared with those observed in canine studies, and these are compared with distributions of naturally occurring osteosarcomas in both species. In the Mayak workers, 29% and 71% of the osteosarcomas were in the peripheral and central skeleton, respectively, with the spine having the most tumors (36%). An almost identical distribution of plutonium-induced osteosarcomas was reported for dogs injected with 239Pu as young adults. This distribution of osteosarcomas is quite different from the distributions of naturally occurring osteosarcomas for both species. In the Cooperative Osteosarcoma Study Group in humans (1,736 osteosarcomas from all ages), over 91% of the tumors occurred in the peripheral skeleton. In the Mayo Clinic group of older individuals (>40 years old), over 60% of the osteosarcomas appeared in the peripheral skeleton. The distribution of naturally occurring osteosarcomas in the canine is similar to that in the adult human. The similarities of the distributions of plutonium-associated osteosarcomas in the Mayak workers with those found in experimental studies suggest that many of the reported osteosarcomas may have been associated with plutonium exposures. These results also support the experimental paradigm that plutonium osteosarcomas have a preference for well vascularized cancellous bone sites. These sites have a greater initial deposition of plutonium, but also greater turnover due to elevated bone remodeling rates.

Adolescent↗
PubMed2002

Osteosarcoma as a second malignant neoplasm.

PURPOSE: The aim of this study is to compare primary and secondary osteosarcomas using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. METHODS: Osteosarcoma cases were identified in the SEER Cancer Incidence Public-Use Database, 1973-96 (1,511 primary and 133 secondary osteosarcomas). Secondary osteosarcomas were further classified as occurring within or outside the previously irradiated field. Comparisons among groups were performed by nominal logistic regression. Survival analyses were performed using Kaplan-Meir and proportional hazards regression. RESULTS: Secondary osteosarcomas were more likely to have a non-extremity primary site and an older age at diagnosis (>40 years) (<0.0001 for both). Secondary osteosarcoma cases continued to be more likely to have a non-extremity site when excluding those occurring within the radiation field. Five-year overall survival was 50% lower for secondary osteosarcomas for both extremity and non-extremity sites. Primary malignancies associated with secondary osteosarcomas included 14 lymphomas/leukemias, six sarcomas, 54 carcinomas, and seven other cancers. Secondary osteosarcomas occurring within a field of radiation were more likely to occur at a younger age, have a malignancy with a primary morphology other than carcinoma, a non-limb site, and a longer duration between their primary malignant neoplasms and the development of osteosarcoma. No difference in the overall survival was noted between secondary osteosarcomas occurring within an irradiated field and those that did not. CONCLUSIONS: Secondary osteosarcomas are associated with carcinomas especially in the elderly. Although a 50% decreased 5-year survival was observed for secondary osteosarcomas in this study, this might not reflect the current outcomes with more aggressive therapy.

Adolescent↗